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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females

Author(s): Mohammad I. Yatoo, Ghaith A. Bahader, Shafayat A. Beigh, Adil M. Khan, Antonisamy William James, Maleha R. Asmi and Zahoor A. Shah*

Volume 23, Issue 7, 2024

Published on: 27 September, 2023

Page: [906 - 916] Pages: 11

DOI: 10.2174/1871527323666230817102125

Price: $65

Abstract

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and longterm outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI. Female animals in preclinical studies and women in clinical trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a favorable protective nature of the females compared to the males, primarily attributed to various protective mechanisms that provide better prognosis and recovery in the females after TBI. Understanding the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological, hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the protective nature of females compared to males. Furthermore, we sought to outline the evidence of multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology, and treatment and which can serve as objective measures and novel targets for individualized therapeutic interventions in TBI treatment. Implementations from this review are important for the understanding of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response in females. It also emphasizes the critical need to include females as a biological variable and in sufficient numbers in future TBI studies.

Keywords: Traumatic brain injury, biomarkers, female, sex differences, protective response, BDNF, mitochondrial.

[1]
Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths-United States, 2007 and 2013. MMWR Surveill Summ 2017; 66(9): 1-16.
[http://dx.doi.org/10.15585/mmwr.ss6609a1] [PMID: 28301451]
[2]
Esterov D, Bellamkonda E, Mandrekar J, Ransom JE, Brown AW. Cause of death after traumatic brain injury: A population-based health record review analysis referenced for nonhead trauma. Neuroepidemiology 2021; 55(3): 180-7.
[http://dx.doi.org/10.1159/000514807] [PMID: 33839727]
[3]
Blaya MO, Raval AP, Bramlett HM. Traumatic brain injury in women across lifespan. Neurobiol Dis 2022; 164: 105613.
[http://dx.doi.org/10.1016/j.nbd.2022.105613] [PMID: 34995753]
[4]
Coronado VG, McGuire LC, Sarmiento K, et al. Trends in traumatic brain injury in the U.S. and the public health response: 1995–2009. J Safety Res 2012; 43(4): 299-307.
[http://dx.doi.org/10.1016/j.jsr.2012.08.011] [PMID: 23127680]
[5]
Gupte RP, Brooks WM, Vukas RR, Pierce JD, Harris JL. Sex differences in traumatic brain injury: What we know and what we should know. J Neurotrauma 2019; 36(22): 3063-91.
[http://dx.doi.org/10.1089/neu.2018.6171] [PMID: 30794028]
[6]
Späni CB, Braun DJ, Van Eldik LJ. Sex-related responses after traumatic brain injury: Considerations for preclinical modeling. Front Neuroendocrinol 2018; 50: 52-66.
[http://dx.doi.org/10.1016/j.yfrne.2018.03.006] [PMID: 29753798]
[7]
Currier Thomas T, Bromberg C, Krishna G. Female sex in experimental traumatic brain injury research: Forging a path forward. Neural Regen Res 2022; 17(3): 550-2.
[http://dx.doi.org/10.4103/1673-5374.316602] [PMID: 34380885]
[8]
Valera EM, Joseph ALC, Snedaker K, et al. Understanding traumatic brain injury in females: A state-of-the-art summary and future directions. J Head Trauma Rehabil 2021; 36(1): E1-E17.
[http://dx.doi.org/10.1097/HTR.0000000000000652] [PMID: 33369993]
[9]
Blennow K, Brody DL, Kochanek PM, et al. Traumatic brain injuries. Nat Rev Dis Primers 2016; 2(1): 16084.
[http://dx.doi.org/10.1038/nrdp.2016.84] [PMID: 27853132]
[10]
Saatman KE, Duhaime AC, Bullock R, Maas AIR, Valadka A, Manley GT. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25(7): 719-38.
[http://dx.doi.org/10.1089/neu.2008.0586] [PMID: 18627252]
[11]
Wilson L, Stewart W, Dams-O’Connor K, et al. The chronic and evolving neurological consequences of traumatic brain injury. Lancet Neurol 2017; 16(10): 813-25.
[http://dx.doi.org/10.1016/S1474-4422(17)30279-X] [PMID: 28920887]
[12]
Ray SK, Dixon CE, Banik NL. Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol 2002; 17(4): 1137-52.
[PMID: 12371142]
[13]
Ng SY, Lee AYW. Traumatic brain injuries: Pathophysiology and potential therapeutic targets. Front Cell Neurosci 2019; 13: 528.
[http://dx.doi.org/10.3389/fncel.2019.00528] [PMID: 31827423]
[14]
Ma C, Wu X, Shen X, et al. Sex differences in traumatic brain injury: A multi-dimensional exploration in genes, hormones, cells, individuals, and society. Chin Neurosurg J 2019; 5: 1-9.
[15]
Rubin TG, Lipton ML. Sex differences in animal models of traumatic brain injury. J Exp Neurosci 2019; 13.
[http://dx.doi.org/10.1177/1179069519844020] [PMID: 31205421]
[16]
Munivenkatappa A, Agrawal A, Shukla D, Kumaraswamy D, Devi B. Traumatic brain injury: Does gender influence outcomes? Int J Crit Illn Inj Sci 2016; 6(2): 70-3.
[http://dx.doi.org/10.4103/2229-5151.183024] [PMID: 27308254]
[17]
Biegon A. Considering biological sex in traumatic brain injury. Front Neurol 2021; 12: 576366.
[http://dx.doi.org/10.3389/fneur.2021.576366] [PMID: 33643182]
[18]
Dennis YR. Alternative models of government-nonprofit sector relations: Theoretical and international perspectives. Nonprofit Volunt Sect Q 2000; 29(1): 149-72.
[19]
Coyle PK. What can we learn from sex differences in MS? J Pers Med 2021; 11(10): 1006.
[http://dx.doi.org/10.3390/jpm11101006] [PMID: 34683148]
[20]
Safi NV, Krieger S. Men with multiple sclerosis. Pract Neurol 2021; 37-40.
[21]
Golden LC, Voskuhl R. The importance of studying sex differences in disease: The example of multiple sclerosis. J Neurosci Res 2017; 95(1-2): 633-43.
[http://dx.doi.org/10.1002/jnr.23955] [PMID: 27870415]
[22]
Villapol S, Loane DJ, Burns MP. Sexual dimorphism in the inflammatory response to traumatic brain injury. Glia 2017; 65(9): 1423-38.
[http://dx.doi.org/10.1002/glia.23171] [PMID: 28608978]
[23]
Brotfain E, Gruenbaum SE, Boyko M, Kutz R, Zlotnik A, Klein M. Neuroprotection by estrogen and progesterone in traumatic brain injury and spinal cord injury. Curr Neuropharmacol 2016; 14(6): 641-53.
[http://dx.doi.org/10.2174/1570159X14666160309123554] [PMID: 26955967]
[24]
Roof RL, Duvdevani R, Braswell L, Stein DG. Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Exp Neurol 1994; 129(1): 64-9.
[http://dx.doi.org/10.1006/exnr.1994.1147] [PMID: 7925843]
[25]
Haider AH, Crompton JG, Chang DC, et al. Evidence of hormonal basis for improved survival among females with trauma-associated shock: An analysis of the National Trauma Data Bank. J Trauma 2010; 69(3): 537-40.
[http://dx.doi.org/10.1097/TA.0b013e3181efc67b] [PMID: 20838123]
[26]
Myrga JM, Failla MD, Ricker JH, et al. A dopamine pathway gene risk score for cognitive recovery following traumatic brain injury: Methodological considerations, preliminary findings, and interactions with sex. J Head Trauma Rehabil 2016; 31(5): E15-29.
[http://dx.doi.org/10.1097/HTR.0000000000000199] [PMID: 26580694]
[27]
Kövesdi E, Szabó-Meleg E, Abrahám IM. The role of estradiol in traumatic brain injury: Mechanism and treatment potential. Int J Mol Sci 2020; 22(1): 11.
[http://dx.doi.org/10.3390/ijms22010011] [PMID: 33374952]
[28]
Günther M, Plantman S, Davidsson J, Angéria M, Mathiesen T, Risling M. COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats. Acta Neurochir 2015; 157(4): 649-59.
[http://dx.doi.org/10.1007/s00701-014-2331-2] [PMID: 25597483]
[29]
Lazarus RC, Buonora JE, Jacobowitz DM, Mueller GP. Protein carbonylation after traumatic brain injury: Cell specificity, regional susceptibility, and gender differences. Free Radic Biol Med 2015; 78: 89-100.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.507] [PMID: 25462645]
[30]
Moore EE, Moore HB, Kornblith LZ, et al. Author correction: Trauma-induced coagulopathy. Nat Rev Dis Primers 2022; 8(1): 25.
[http://dx.doi.org/10.1038/s41572-022-00360-y] [PMID: 35459275]
[31]
Chiaretti A, Antonelli A, Riccardi R, et al. Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children. Eur J Paediatr Neurol 2008; 12(3): 195-204.
[http://dx.doi.org/10.1016/j.ejpn.2007.07.016] [PMID: 17881264]
[32]
Xiong Y, Mahmood A, Lu D, et al. Role of gender in outcome after traumatic brain injury and therapeutic effect of erythropoietin in mice. Brain Res 2007; 1185: 301-12.
[http://dx.doi.org/10.1016/j.brainres.2007.09.052] [PMID: 17976541]
[33]
Hall ED, Pazara KE, Linseman KL. Sex differences in postischemic neuronal necrosis in gerbils. J Cereb Blood Flow Metab 1991; 11(2): 292-8.
[http://dx.doi.org/10.1038/jcbfm.1991.61] [PMID: 1997500]
[34]
Bayir H, Marion DW, Puccio AM, et al. Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. J Neurotrauma 2004; 21(1): 1-8.
[http://dx.doi.org/10.1089/089771504772695896] [PMID: 14987460]
[35]
Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó FV, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 2003; 34(5): 546-52.
[http://dx.doi.org/10.1016/S0891-5849(02)01356-4] [PMID: 12614843]
[36]
Duncan KA, Garijo-Garde S. Sex, genes, and traumatic brain injury (TBI): A call for a gender inclusive approach to the study of TBI in the lab. Front Neurosci 2021; 15: 681599.
[http://dx.doi.org/10.3389/fnins.2021.681599] [PMID: 34025346]
[37]
Demarest TG, McCarthy MM. Sex differences in mitochondrial (dys)function: Implications for neuroprotection. J Bioenerg Biomembr 2015; 47(1-2): 173-88.
[http://dx.doi.org/10.1007/s10863-014-9583-7] [PMID: 25293493]
[38]
Gaignard P, Savouroux S, Liere P, et al. Effect of sex differences on brain mitochondrial function and its suppression by ovariectomy and in aged mice. Endocrinology 2015; 156(8): 2893-904.
[http://dx.doi.org/10.1210/en.2014-1913] [PMID: 26039154]
[39]
Scott MC, Prabhakara KS, Walters AJ, Olson SD, Cox CS Jr. Determining sex-based differences in inflammatory response in an experimental traumatic brain injury model. Front Immunol 2022; 13: 753570.
[http://dx.doi.org/10.3389/fimmu.2022.753570] [PMID: 35222368]
[40]
Mollayeva T, Mollayeva S, Pacheco N, Colantonio A. Systematic review of sex and gender effects in traumatic brain injury: Equity in clinical and functional outcomes. Front Neurol 2021; 12: 678971.
[http://dx.doi.org/10.3389/fneur.2021.678971] [PMID: 34566834]
[41]
Ruigrok ANV, Salimi-Khorshidi G, Lai MC, et al. A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev 2014; 39(100): 34-50.
[http://dx.doi.org/10.1016/j.neubiorev.2013.12.004] [PMID: 24374381]
[42]
Klabunde M, Weems CF, Raman M, Carrion VG. The moderating effects of sex on insula subdivision structure in youth with posttraumatic stress symptoms. Depress Anxiety 2017; 34(1): 51-8.
[http://dx.doi.org/10.1002/da.22577] [PMID: 27862643]
[43]
Bramlett HM, Dietrich WD. Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J Neurotrauma 2001; 18(9): 891-900.
[http://dx.doi.org/10.1089/089771501750451811] [PMID: 11565601]
[44]
Roof RL, Duvdevani R, Stein DG. Gender influences outcome of brain injury: Progesterone plays a protective role. Brain Res 1993; 607(1-2): 333-6.
[http://dx.doi.org/10.1016/0006-8993(93)91526-X] [PMID: 8481809]
[45]
Dollé JP, Jaye A, Anderson SA, Ahmadzadeh H, Shenoy VB, Smith DH. Newfound sex differences in axonal structure underlie differential outcomes from in vitro traumatic axonal injury. Exp Neurol 2018; 300: 121-34.
[http://dx.doi.org/10.1016/j.expneurol.2017.11.001] [PMID: 29104114]
[46]
Spychala MS, Honarpisheh P, McCullough LD. Sex differences in neuroinflammation and neuroprotection in ischemic stroke. J Neurosci Res 2017; 95(1-2): 462-71.
[http://dx.doi.org/10.1002/jnr.23962] [PMID: 27870410]
[47]
Coates BM, Vavilala MS, Mack CD, et al. Influence of definition and location of hypotension on outcome following severe pediatric traumatic brain injury. Crit Care Med 2005; 33(11): 2645-50.
[http://dx.doi.org/10.1097/01.CCM.0000186417.19199.9B] [PMID: 16276192]
[48]
O’Connor C, Cernak I, Vink R. The temporal profile of edema formation differs between male and female rats following diffuse traumatic brain injury. Proceedings of the Brain Edema XIII. Ann Arbor, Michigan, USA. 2006; pp. 121-4.
[http://dx.doi.org/10.1007/3-211-30714-1_27]
[49]
Cash A, Theus MH. Mechanisms of blood–brain barrier dysfunction in traumatic brain injury. Int J Mol Sci 2020; 21(9): 3344.
[http://dx.doi.org/10.3390/ijms21093344] [PMID: 32397302]
[50]
Russell AL, Richardson MR, Bauman BM, et al. Differential responses of the HPA axis to mild blast traumatic brain injury in male and female mice. Endocrinology 2018; 159(6): 2363-75.
[http://dx.doi.org/10.1210/en.2018-00203] [PMID: 29701827]
[51]
Dash PK, Hergenroeder GW, Jeter CB, Choi HA, Kobori N, Moore AN. Traumatic brain injury alters methionine metabolism: Implications for pathophysiology. Front Syst Neurosci 2016; 10: 36.
[http://dx.doi.org/10.3389/fnsys.2016.00036] [PMID: 27199685]
[52]
Shahrokhi N, Khaksari M, Soltani Z, Mahmoodi M, Nakhaee N. Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury. Can J Physiol Pharmacol 2010; 88(4): 414-21.
[http://dx.doi.org/10.1139/Y09-126] [PMID: 20555409]
[53]
Ransohoff RM, Perry VH. Microglial physiology: Unique stimuli, specialized responses. Annu Rev Immunol 2009; 27(1): 119-45.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132528] [PMID: 19302036]
[54]
Kalimon OJ, Sullivan PG. Sex differences in mitochondrial function following a controlled cortical impact traumatic brain injury in rodents. Front Mol Neurosci 2021; 14: 753946.
[http://dx.doi.org/10.3389/fnmol.2021.753946] [PMID: 34720875]
[55]
Roof RL, Duvdevani R, Heyburn JW, Stein DG. Progesterone rapidly decreases brain edema: Treatment delayed up to 24 hours is still effective. Exp Neurol 1996; 138(2): 246-51.
[http://dx.doi.org/10.1006/exnr.1996.0063] [PMID: 8620923]
[56]
O’Connor CA, Cernak I, Vink R. Both estrogen and progesterone attenuate edema formation following diffuse traumatic brain injury in rats. Brain Res 2005; 1062(1-2): 171-4.
[http://dx.doi.org/10.1016/j.brainres.2005.09.011] [PMID: 16256079]
[57]
Taylor AN, Tio DL, Paydar A, Sutton RL. Sex differences in thermal, stress, and inflammatory responses to minocycline administration in rats with traumatic brain injury. J Neurotrauma 2018; 35(4): 630-8.
[http://dx.doi.org/10.1089/neu.2017.5238] [PMID: 29179648]
[58]
Armstead WM, Vavilala MS. Adrenomedullin reduces gender-dependent loss of hypotensive cerebrovasodilation after newborn brain injury through activation of ATP-dependent K channels. J Cereb Blood Flow Metab 2007; 27(10): 1702-9.
[http://dx.doi.org/10.1038/sj.jcbfm.9600473] [PMID: 17377515]
[59]
Armstead WM, Kiessling JW, Bdeir K, Kofke WA, Vavilala MS. Adrenomedullin prevents sex-dependent impairment of autoregulation during hypotension after piglet brain injury through inhibition of ERK MAPK upregulation. J Neurotrauma 2010; 27(2): 391-402.
[http://dx.doi.org/10.1089/neu.2009.1094] [PMID: 20170313]
[60]
Armstead WM, Kiessling JW, Riley J, Kofke WA, Vavilala MS. Phenylephrine infusion prevents impairment of ATP- and calcium-sensitive potassium channel-mediated cerebrovasodilation after brain injury in female, but aggravates impairment in male, piglets through modulation of ERK MAPK upregulation. J Neurotrauma 2011; 28(1): 105-11.
[http://dx.doi.org/10.1089/neu.2010.1581] [PMID: 20964536]
[61]
Armstead WM, Riley J, Vavilala MS. TBI sex dependently upregulates ET-1 to impair autoregulation, which is aggravated by phenylephrine in males but is abrogated in females. J Neurotrauma 2012; 29(7): 1483-90.
[http://dx.doi.org/10.1089/neu.2011.2248] [PMID: 22335188]
[62]
Armstead WM, Kiessling JW, Kofke WA, Vavilala MS. Impaired cerebral blood flow autoregulation during postraumatic arterial hypotension after fluid percussion brain injury is prevented by phenylephrine in female but exacerbated in male piglets by ERK MAPK upregulation. Crit Care Med 2010; 38: 1868.
[http://dx.doi.org/10.1097/CCM.0b013e3181e8ac1a] [PMID: 20562700]
[63]
Roof RL, Hall ED. Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J Neurotrauma 2000; 17(12): 1155-69.
[http://dx.doi.org/10.1089/neu.2000.17.1155] [PMID: 11186229]
[64]
Geddes RI, Peterson BL, Stein DG, Sayeed I. Progesterone treatment shows benefit in female rats in a pediatric model of controlled cortical impact injury. PLoS One 2016; 11(1): e0146419.
[http://dx.doi.org/10.1371/journal.pone.0146419] [PMID: 26799561]
[65]
Free KE, Greene AM, Bondi CO, Lajud N, de la Tremblaye PB, Kline AE. Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury. Exp Neurol 2017; 296: 62-8.
[http://dx.doi.org/10.1016/j.expneurol.2017.07.004] [PMID: 28698031]
[66]
Meffre D, Pianos A, Liere P, et al. Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: Analysis by gas chromatography/mass spectrometry. Endocrinology 2007; 148(5): 2505-17.
[http://dx.doi.org/10.1210/en.2006-1678] [PMID: 17303653]
[67]
Bramlett HM, Furones-Alonso O, Lotocki G, Rodriguez-Paez A, Sanchez-Molano J, Keane RW. Sex differences in XIAP cleavage after traumatic brain injury in the rat. Neurosci Lett 2009; 461(1): 49-53.
[http://dx.doi.org/10.1016/j.neulet.2009.05.071] [PMID: 19500649]
[68]
Oconnor C, Cernak I, Johnson F, Vink R. Effects of progesterone on neurologic and morphologic outcome following diffuse traumatic brain injury in rats. Exp Neurol 2007; 205(1): 145-53.
[http://dx.doi.org/10.1016/j.expneurol.2007.01.034] [PMID: 17362936]
[69]
Raghava N, Das BC, Ray SK. Neuroprotective effects of estrogen in CNS injuries: Insights from animal models. Neurosci Neuroecon 2017; 6: 15-29.
[http://dx.doi.org/10.2147/NAN.S105134] [PMID: 28845391]
[70]
Espinoza TR, Wright DW. The role of progesterone in traumatic brain injury. J Head Trauma Rehabil 2011; 26(6): 497-9.
[http://dx.doi.org/10.1097/HTR.0b013e31823088fa] [PMID: 22088981]
[71]
Clevenger AC, Kim H, Salcedo E, et al. Endogenous sex steroids dampen neuroinflammation and improve outcome of traumatic brain injury in mice. J Mol Neurosci 2018; 64(3): 410-20.
[http://dx.doi.org/10.1007/s12031-018-1038-x] [PMID: 29450697]
[72]
Ramos-Martinez E, Ramos-Martínez I, Molina-Salinas G, Zepeda-Ruiz WA, Cerbon M. The role of prolactin in central nervous system inflammation. Rev Neurosci 2021; 32(3): 323-40.
[http://dx.doi.org/10.1515/revneuro-2020-0082] [PMID: 33661585]
[73]
Weil ZM, White B, Whitehead B, Karelina K. The role of the stress system in recovery after traumatic brain injury: A tribute to Bruce S. McEwen. Neurobiol Stress 2022; 19: 100467.
[http://dx.doi.org/10.1016/j.ynstr.2022.100467] [PMID: 35720260]
[74]
Liu YY, Brent GA. Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury. Pharmacol Ther 2018; 186: 176-85.
[http://dx.doi.org/10.1016/j.pharmthera.2018.01.007] [PMID: 29378220]
[75]
Wagner AK, Bayir H, Ren D, Puccio A, Zafonte RD, Kochanek PM. Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: The impact of gender, age, and hypothermia. J Neurotrauma 2004; 21(2): 125-36.
[http://dx.doi.org/10.1089/089771504322778596] [PMID: 15000754]
[76]
Wagner AK, Chen X, Kline AE, Li Y, Zafonte RD, Dixon CE. Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury. Exp Neurol 2005; 195(2): 475-83.
[http://dx.doi.org/10.1016/j.expneurol.2005.06.009] [PMID: 16023635]
[77]
Gasco V, Cambria V, Bioletto F, Ghigo E, Grottoli S. Traumatic brain injury as frequent cause of hypopituitarism and growth hormone deficiency: Epidemiology, diagnosis, and treatment. Front Endocrinol 2021; 12: 634415.
[http://dx.doi.org/10.3389/fendo.2021.634415] [PMID: 33790864]
[78]
Acaz-Fonseca E, Avila-Rodriguez M, Garcia-Segura LM, Barreto GE. Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions. Prog Neurobiol 2016; 144: 5-26.
[http://dx.doi.org/10.1016/j.pneurobio.2016.06.002] [PMID: 27283249]
[79]
Duncan KA. Estrogen formation and inactivation following TBI: What we know and where we could go. Front Endocrinol 2020; 11: 345.
[http://dx.doi.org/10.3389/fendo.2020.00345] [PMID: 32547495]
[80]
Cox A, Varma A, Barry J, Vertegel A, Banik N. Nanoparticle estrogen in rat spinal cord injury elicits rapid anti-inflammatory effects in plasma, cerebrospinal fluid, and tissue. J Neurotrauma 2015; 32(18): 1413-21.
[http://dx.doi.org/10.1089/neu.2014.3730] [PMID: 25845398]
[81]
Hill RA, Chua HK, Jones MEE, Simpson ER, Boon WC. Estrogen deficiency results in apoptosis in the frontal cortex of adult female aromatase knockout mice. Mol Cell Neurosci 2009; 41(1): 1-7.
[http://dx.doi.org/10.1016/j.mcn.2008.12.009] [PMID: 19185610]
[82]
Culmsee C, Vedder H, Ravati A, et al. Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: Evidence for a receptor-independent antioxidative mechanism. J Cereb Blood Flow Metab 1999; 19(11): 1263-9.
[http://dx.doi.org/10.1097/00004647-199911000-00011] [PMID: 10566973]
[83]
Brann DW, Dhandapani K, Wakade C, Mahesh VB, Khan MM. Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications. Steroids 2007; 72(5): 381-405.
[http://dx.doi.org/10.1016/j.steroids.2007.02.003] [PMID: 17379265]
[84]
Cimarosti H, O’Shea RD, Jones NM, et al. The effects of estradiol on estrogen receptor and glutamate transporter expression in organotypic hippocampal cultures exposed to oxygen-glucose deprivation. Neurochem Res 2006; 31(4): 483-90.
[http://dx.doi.org/10.1007/s11064-006-9043-9] [PMID: 16758356]
[85]
Kemper MF, Stirone C, Krause DN, Duckles SP, Procaccio V. Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection. Eur J Pharmacol 2014; 723: 322-9.
[http://dx.doi.org/10.1016/j.ejphar.2013.11.009] [PMID: 24275351]
[86]
Wei J, Xiao G. The neuroprotective effects of progesterone on traumatic brain injury: Current status and future prospects. Acta Pharmacol Sin 2013; 34(12): 1485-90.
[http://dx.doi.org/10.1038/aps.2013.160] [PMID: 24241345]
[87]
Lopez-Rodriguez AB, Acaz-Fonseca E, Giatti S, et al. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice. Psychoneuroendocrinology 2015; 56: 1-11.
[http://dx.doi.org/10.1016/j.psyneuen.2015.02.018] [PMID: 25770855]
[88]
Webster KM, Wright DK, Sun M, et al. Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury. J Neuroinflammation 2015; 12(1): 238.
[http://dx.doi.org/10.1186/s12974-015-0457-7] [PMID: 26683475]
[89]
Garay L, Deniselle MCG, Lima A, Roig P, De Nicola AF. Effects of progesterone in the spinal cord of a mouse model of multiple sclerosis. J Steroid Biochem Mol Biol 2007; 107(3-5): 228-37.
[http://dx.doi.org/10.1016/j.jsbmb.2007.03.040] [PMID: 17692515]
[90]
Stein DG, Wright DW. Progesterone in the clinical treatment of acute traumatic brain injury. Expert Opin Investig Drugs 2010; 19(7): 847-57.
[http://dx.doi.org/10.1517/13543784.2010.489549] [PMID: 20486864]
[91]
Chen G, Shi J, Ding Y, Yin H, Hang C. Progesterone prevents traumatic brain injury-induced intestinal nuclear factor kappa B activation and proinflammatory cytokines expression in male rats. Mediat Inflamm 2007; 20074: 93431.
[http://dx.doi.org/10.1155/2007/93431]
[92]
Lei B, Mace B, Dawson HN, Warner DS, Laskowitz DT, James ML. Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia. PLoS One 2014; 9(7): e103969.
[http://dx.doi.org/10.1371/journal.pone.0103969] [PMID: 25080336]
[93]
Zlotnik A, Gurevich B, Tkachov S, Maoz I, Shapira Y, Teichberg VI. Brain neuroprotection by scavenging blood glutamate. Exp Neurol 2007; 203(1): 213-20.
[http://dx.doi.org/10.1016/j.expneurol.2006.08.021] [PMID: 17014847]
[94]
Robertson CL, Puskar A, Hoffman GE, Murphy AZ, Saraswati M, Fiskum G. Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats. Exp Neurol 2006; 197(1): 235-43.
[http://dx.doi.org/10.1016/j.expneurol.2005.09.014] [PMID: 16259981]
[95]
Reyes-Mendoza J, Morales T. Post-treatment with prolactin protects hippocampal CA1 neurons of the ovariectomized female rat against kainic acid-induced neurodegeneration. Neuroscience 2016; 328: 58-68.
[http://dx.doi.org/10.1016/j.neuroscience.2016.04.030] [PMID: 27126559]
[96]
Yousefvand S, Hadjzadeh MA, Keshavarzi Z, et al. Effects of prolactin on movement disorders and APOE, GFAP, and PRL receptor gene expression following intracerebral hemorrhage in rats. Iran J Basic Med Sci 2021; 24(12): 1709-16.
[PMID: 35432801]
[97]
Scranton R, Baskin D. Impaired pituitary axes following traumatic brain injury. J Clin Med 2015; 4(7): 1463-79.
[http://dx.doi.org/10.3390/jcm4071463] [PMID: 26239686]
[98]
Zhu Z, Yan J, Geng C, et al. A polymorphism Within the 3′ UTR of NLRP3 is associated with susceptibility for ischemic stroke in chinese population. Cell Mol Neurobiol 2016; 36(6): 981-8.
[http://dx.doi.org/10.1007/s10571-015-0288-1] [PMID: 26689701]
[99]
Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): Randomised placebo-controlled trial. Lancet 2004; 364(9442): 1321-8.
[http://dx.doi.org/10.1016/S0140-6736(04)17188-2] [PMID: 15474134]
[100]
Talhada D, Santos CRA, Gonçalves I, Ruscher K. Thyroid hormones in the brain and their impact in recovery mechanisms after stroke. Front Neurol 2019; 10: 1103.
[http://dx.doi.org/10.3389/fneur.2019.01103] [PMID: 31681160]
[101]
Mele C, Pagano L, Franciotta D, et al. Thyroid function in the subacute phase of traumatic brain injury: A potential predictor of post-traumatic neurological and functional outcomes. J Endocrinol Invest 2022; 45(2): 379-89.
[http://dx.doi.org/10.1007/s40618-021-01656-8] [PMID: 34351610]
[102]
Morissette M, Di Paolo T. Sex and estrous cycle variations of rat striatal dopamine uptake sites. Neuroendocrinology 1993; 58(1): 16-22.
[http://dx.doi.org/10.1159/000126507] [PMID: 8264850]
[103]
Küppers E, Ivanova T, Karolczak M, Beyer C. Estrogen: A multifunctional messenger to nigrostriatal dopaminergic neurons. J Neurocytol 2000; 29(5/6): 375-85.
[http://dx.doi.org/10.1023/A:1007165307652] [PMID: 11424954]
[104]
Di Battista AP, Rhind SG, Churchill N, Richards D, Lawrence DW, Hutchison MG. Peripheral blood neuroendocrine hormones are associated with clinical indices of sport-related concussion. Sci Rep 2019; 9(1): 18605.
[http://dx.doi.org/10.1038/s41598-019-54923-3] [PMID: 31819094]
[105]
Moore EE, Moore HB, Kornblith LZ, et al. Trauma-induced coagulopathy. Nat Rev Dis Primers 2021; 7(1): 30.
[http://dx.doi.org/10.1038/s41572-021-00264-3] [PMID: 33927200]
[106]
Zhu C, Wang S, Wang B, et al. 17β-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling pathways to suppress light-induced degeneration in rat retina. Neuroscience 2015; 304: 328-39.
[http://dx.doi.org/10.1016/j.neuroscience.2015.07.057] [PMID: 26211446]
[107]
Balthazart J, Stoop R, Foidart A, Granneman JCM, Lambert JGD. Distribution and regulation of estrogen-2-hydroxylase in the quail brain. Brain Res Bull 1994; 35(4): 339-45.
[http://dx.doi.org/10.1016/0361-9230(94)90111-2] [PMID: 7850484]
[108]
Han D, Scott EL, Dong Y, Raz L, Wang R, Zhang Q. Attenuation of mitochondrial and nuclear p38α signaling: A novel mechanism of estrogen neuroprotection in cerebral ischemia. Mol Cell Endocrinol 2015; 400: 21-31.
[http://dx.doi.org/10.1016/j.mce.2014.11.010] [PMID: 25462588]
[109]
Leitman DC, Paruthiyil S, Vivar OI, et al. Regulation of specific target genes and biological responses by estrogen receptor subtype agonists. Curr Opin Pharmacol 2010; 10(6): 629-36.
[http://dx.doi.org/10.1016/j.coph.2010.09.009] [PMID: 20951642]
[110]
Koos RD. Minireview: Putting physiology back into estrogens’ mechanism of action. Endocrinology 2011; 152(12): 4481-8.
[http://dx.doi.org/10.1210/en.2011-1449] [PMID: 21952239]
[111]
Almadhidi J, Moslemi S, Drosdowsky MA, Séralini GE. Equine cytochrome P450 aromatase exhibits an estrogen 2-hydroxylase activity in vitro. J Steroid Biochem Mol Biol 1996; 59(1): 55-61.
[http://dx.doi.org/10.1016/S0960-0760(96)00085-4] [PMID: 9009238]
[112]
Purohit A, Potter BVL, Parker MG, Reed MJ. Steroid sulphatase: Expression, isolation and inhibition for active-site identification studies. Chem Biol Interact 1998; 109(1-3): 183-93.
[http://dx.doi.org/10.1016/S0009-2797(97)00132-4] [PMID: 9566745]
[113]
Kim H, Yu T, Cam-Etoz B, van Groen T, Hubbard WJ, Chaudry IH. Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model. J Neurosurg 2017; 127(1): 23-31.
[http://dx.doi.org/10.3171/2016.7.JNS161263] [PMID: 27662529]
[114]
Schumacher M, Hussain R, Gago N, Oudinet JP, Mattern C, Ghoumari AM. Progesterone synthesis in the nervous system: Implications for myelination and myelin repair. Front Neurosci 2012; 6: 10.
[http://dx.doi.org/10.3389/fnins.2012.00010] [PMID: 22347156]
[115]
Ismail H, Shakkour Z, Tabet M, et al. Traumatic brain injury: Oxidative stress and novel anti-oxidants such as mitoquinone and edaravone. Antioxidants 2020; 9(10): 943.
[http://dx.doi.org/10.3390/antiox9100943] [PMID: 33019512]
[116]
Di Pietro V, Yakoub KM, Caruso G, et al. Antioxidant therapies in traumatic brain injury. Antioxidants 2020; 9(3): 260.
[http://dx.doi.org/10.3390/antiox9030260] [PMID: 32235799]
[117]
Bruce-Keller AJ, Dimayuga FO, Reed JL, et al. Gender and estrogen manipulation do not affect traumatic brain injury in mice. J Neurotrauma 2007; 24(1): 203-15.
[http://dx.doi.org/10.1089/neu.2006.0163] [PMID: 17263684]
[118]
Acaz-Fonseca E, Duran JC, Carrero P, Garcia-Segura LM, Arevalo MA. Sex differences in glia reactivity after cortical brain injury. Glia 2015; 63(11): 1966-81.
[http://dx.doi.org/10.1002/glia.22867] [PMID: 26037411]
[119]
Doran SJ, Ritzel RM, Glaser EP, Henry RJ, Faden AI, Loane DJ. Sex differences in acute neuroinflammation after experimental traumatic brain injury are mediated by infiltrating myeloid cells. J Neurotrauma 2019; 36(7): 1040-53.
[http://dx.doi.org/10.1089/neu.2018.6019] [PMID: 30259790]
[120]
Greco T, Vespa PM, Prins ML. Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury. Exp Neurol 2020; 329: 113289.
[http://dx.doi.org/10.1016/j.expneurol.2020.113289] [PMID: 32247790]
[121]
Gray JD, Milner TA, McEwen BS. Dynamic plasticity: The role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors. Neuroscience 2013; 239: 214-27.
[http://dx.doi.org/10.1016/j.neuroscience.2012.08.034] [PMID: 22922121]
[122]
Chen X, Li Y, Kline AE, Dixon CE, Zafonte RD, Wagner AK. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury. Neuroscience 2005; 135(1): 11-7.
[http://dx.doi.org/10.1016/j.neuroscience.2005.05.041] [PMID: 16084663]
[123]
Lan Y-L, Li S, Lou J-C, Ma X-C, Zhang B. The potential roles of dopamine in traumatic brain injury: A preclinical and clinical update. Am J Transl Res 2019; 11(5): 2616-31.
[PMID: 31217842]
[124]
Öst M, Nylén K, Csajbok L, Blennow K, Rosengren L, Nellgård B. Apolipoprotein E polymorphism and gender difference in outcome after severe traumatic brain injury. Acta Anaesthesiol Scand 2008; 52(10): 1364-9.
[http://dx.doi.org/10.1111/j.1399-6576.2008.01675.x] [PMID: 19025529]
[125]
Huang T, Shu Y, Cai YD. Genetic differences among ethnic groups. BMC Genomics 2015; 16(1): 1093.
[http://dx.doi.org/10.1186/s12864-015-2328-0] [PMID: 26690364]
[126]
Jullienne A, Salehi A, Affeldt B, et al. Male and female mice exhibit divergent responses of the cortical vasculature to traumatic brain injury. J Neurotrauma 2018; 35(14): 1646-58.
[http://dx.doi.org/10.1089/neu.2017.5547] [PMID: 29648973]
[127]
Bromberg CE, Condon AM, Ridgway SW, et al. Sex-dependent pathology in the HPA axis at a sub-acute period after experimental traumatic brain injury. Front Neurol 2020; 11: 946.
[http://dx.doi.org/10.3389/fneur.2020.00946] [PMID: 33101162]
[128]
Fanaei H, Karimian SM, Sadeghipour HR, et al. Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats. Brain Res 2014; 1558: 74-83.
[http://dx.doi.org/10.1016/j.brainres.2014.02.028] [PMID: 24565925]
[129]
Barreto G, Veiga S, Azcoitia I, Garcia-Segura LM, Garcia-Ovejero D. Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: Role of its metabolites, oestradiol and dihydrotestosterone. Eur J Neurosci 2007; 25(10): 3039-46.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05563.x] [PMID: 17561817]
[130]
Toro-Urrego N, Garcia-Segura LM, Echeverria V, Barreto GE. Testosterone protects mitochondrial function and regulates neuroglobin expression in astrocytic cells exposed to glucose deprivation. Front Aging Neurosci 2016; 8: 152.
[http://dx.doi.org/10.3389/fnagi.2016.00152] [PMID: 27445795]
[131]
Bharadwaj VN, Copeland C, Mathew E, et al. Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury. Tissue Eng Part A 2020; 26(13-14): 688-701.
[http://dx.doi.org/10.1089/ten.tea.2020.0040] [PMID: 32697674]
[132]
Yagi S, Galea LAM. Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology 2019; 44(1): 200-13.
[http://dx.doi.org/10.1038/s41386-018-0208-4] [PMID: 30214058]
[133]
Westenbroek C, Den Boer JA, Veenhuis M, Ter Horst GJ. Chronic stress and social housing differentially affect neurogenesis in male and female rats. Brain Res Bull 2004; 64(4): 303-8.
[http://dx.doi.org/10.1016/j.brainresbull.2004.08.006] [PMID: 15561464]

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