Medical Treatment and Neuroprotection in Traumatic Brain Injury

Abstract

The goal of this article is to give an overview about the established current treatment concepts of traumatic brain injury, as well as an outlook on possible future developments in pharmacological neuroprotection. Modern medical treatment modalities of traumatic brain injury (TBI), including the preclinical management of severely head-injured patients, are reviewed. Since an increased intracranial pressure represents the most common complication of severe traumatic brain injury, frequently associated with the development of secondary brain damage, special emphasis was given to an updated treatment algorithm for this important condition. New insight into the pathophysiology of severe traumatic brain injury, especially the realization that brain damage develops sequentially, initiated several new treatment approaches aiming at the interruption of pathophysiological mechanisms leading to secondary brain injury. A high number of pharmacological substances have been tested for their ability to ameliorate secondary damage after TBI, or are currently under clinical trial. Although no drug has achieved this goal so far, the most promising of these therapeutical approaches, glutamate receptor antagonists, calcium channel antagonists, free radical scavengers, and cyclosporin A will be discussed in this review. Although a "magical bullet" for the treatment of traumatic brain injury has not been developed yet, several of the currently investigated neuroprotective strategies seem to be encouraging. A promising future approach might be to evaluate treatment strategies that combine several pharmacological agents, and possibly other treatment modalities, such as mild hypothermia, "tailored" according to the special pathology of patient subgroups, or even to every single patient in order to achieve an improvement in outcome after TBI.

Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo

“…Dantrolene has the great advantage that has passed clinical trials, being already in clinical use for treatment of malignant hypertermia, where it decreases body temperature. However, dantrolene ability to counteract hypertermia would not affect its neuroprotective potential, being known that hypothermia is neuroprotective in several acute neurological diseases [47][48][49][50]. It was also reported that hypothermia protects from neuronal cell death induced by KA [51,52].…”

Potentiation of neurite outgrowth and reduction of apoptosis by immunosuppressive agents: implications for neuronal injury and transplantation

“…7,16 Normally, mitochondria play a major role in the maintenance of intracellular calcium homeostasis. However, when calcium accumulates in the mitochondria after traumatic spinal cord or brain injury, these cell components swell and lose function.…”

“…16,23,26 Cyclosporin A is believed to exert a neuroprotective effect by blocking the mitochondrial permeability transition pore, inhibiting calcineurin, and thereby preserving mitochondrial function and integrity. 7,8 Another immunosuppressive drug, FK506, which is used to prevent allograft rejection in organ transplantation, has been shown to inhibit calcineurin, reduce accumulation of intracellular calcium from inositol 1,4,5-trisphosphate-sensitive stores, suppress caspase activation, and protect against apoptosis. 5,6,17 The other immunosuppressive drug used in this study, dexamethasone, enhances neurotrophin activity and reduces the proapoptotic expression of c-fos and c-jun.…”

Bilateral cortical atrophy after severe brain trauma and extradural homatoma

“…Encouraging therapeutical strategies against secondary brain injury has been investigated in clinical trials 2,10 . However, currently, there is no treatment able to block secondary brain injury and the delayed cerebral atrophy.…”