Title:Pathophysiology of Blood-Brain Barrier in Brain Injury in Cold and Hot Environments: Novel Drug Targets for Neuroprotection
Volume: 15
Issue: 9
Author(s): Hari Shanker Sharma, Dafin F. Muresanu, José V. Lafuente, Ala Nozari, Ranjana Patnaik, Stephen D. Skaper and Aruna Sharma
Affiliation:
Keywords:
Ambient temperature, blood-brain barrier, blunt head injury, brain edema, brain pathology, cognitive dysfunction,
cold exposure, concussion, cortical injury, drug therapy, hot environment, penetrating brain injury, seasonal variations,
traumatic brain injury.
Abstract: The blood-brain barrier (BBB) plays a pivotal role in the maintenance of
central nervous system function in health and disease. Thus, in almost all
neurodegenerative, traumatic or metabolic insults BBB breakdown occurs, allowing
entry of serum proteins into the brain fluid microenvironment with subsequent
edema formation and cellular injury. Accordingly, pharmacological restoration of
BBB function will lead to neurorepair. However, brain injury which occurs
following blast, bullet wounds, or knife injury appears to initiate different sets of
pathophysiological responses. Moreover, other local factors at the time of injury
such as cold or elevated ambient temperatures could also impact the final outcome.
Obviously, drug therapy applied to different kinds of brain trauma occurring at either
cold or hot environments may respond differently. This is largely due to the fact that internal defense
mechanisms of the brain, gene expression, release of neurochemicals and binding of drugs to specific
receptors are affected by external ambient temperature changes. These factors may also affect BBB
function and development of edema formation after brain injury. In this review, the effects of seasonal
exposure to heat and cold on traumatic brain injury using different models i.e., concussive brain injury
and cerebral cortical lesion, on BBB dysfunction in relation to drug therapy are discussed. Our
observations clearly suggest that closed head injury and open brain injury are two different entities and
the external hot or cold environments affect both of them remarkably. Thus, effective pharmacological
therapeutic strategies should be designed with these views in mind, as military personnel often
experience blunt or penetrating head injuries in either cold or hot environments.
