Therapeutic Approaches in Subjects with Brain Lesions

Abstract

The pharmacological treatment of subjects who sustain a brain lesion, either accidentally (trauma, stroke) or surgically (tumor excision, stereotactic lesions, etc.) is generally aimed at preventing further damage from pathology such as edema, hemorrhage, infection, seizures, or renal or cardiopulmonary failure. The efficacy of these treatments can be observed in the period immediately following the insult. However, the long-term effects, if any, of these treatments, or any interactions between the drugs used and mechanisms involved in functional recovery, have often been ignored.

A brief review of some basic aspect of the response of neural and nonneural cells to injury is offered, with some comments on events occurring during histogenesis and in the initiation and regulation of inflammatory and immune responses that might be relevant to the problem of brain plasticity. I then discuss some of the mechanisms of cell damage common to different forms of injury (e.g., trauma, hemorrhage, thrombosis) such as membrane permeability changes, intracellular calcium alterations, and the role of certain neurotransmitters in the genesis of acute neuronal loss. Special emphasis on ischemia is made, with a review of the pharmacological treatment of stroke and comments on the importance of the management of the medical and neurological complications of a brain lesion. I conclude with a discussion of the requirements in the design of clinical trials oriented towards the individualization of drug theraphy.

Finally, I summarize our own investigation with a pharmacological model of reversible brain dysfunction using GABA, an endogenous inhibitory neurotransmitter, in both rats and monkeys.