Neuroprotection for CNS disorders

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released February 9, 2000; last updated March 8, 2017; expires March 8, 2020

Overview

Neuroprotection involves prevention of neuronal death by inhibiting 1 or more of the pathophysiological steps in the processes that follow brain injury or ischemia due to occlusion of a cerebral artery or neurodegenerative processes. This article classifies various neuroprotective agents and describes a few of these. Examples of clinical conditions are given to show application of neuroprotective drugs and nonpharmacological methods.

Key points

 

• The concept of neuroprotection is now important in many diseases that were once only treated symptomatically and in which a disease-modifying approach is desirable.

 

• Neuroprotective agents have an important role in the management of neurodegenerative disorders as well as acute insults such as CNS trauma, cerebral ischemia, and iatrogenic hypoxia/ischemia during surgical procedures.

 

• Neuroprotective strategies are also required to protect the brain against toxic effects of chemicals and drugs.

 

• There are numerous neuroprotective agents from several pharmacological as well as nonpharmaceutical categories as well as those based on intrinsic neuroprotective mechanisms that come into play following injury to the brain.

Historical note and terminology

In the 1960s the term "neuroprotection" was applied to the protection of the brain during high-risk neurosurgical and cardiovascular procedures that required the interruption of blood circulation to the brain. The most significant form of neuroprotection, hypothermia, was initially used for the treatment of head injury in 1943 (Fay 1943). The first pharmacological approach to neuroprotection in severe head injury was intravenous barbiturate therapy. The concept of neuroprotection is linked to the role of free radicals in the etiology of neurologic disorders, particularly stroke and degenerative neurologic disorders. During the 1990s, there was considerable work done on elucidating the pathomechanism of various neurologic disorders and identification of various neurotoxic phenomena. Disorders involving both the brain and the spinal cord were included. Various pharmacological agents were developed to counteract these phenomena. Best known among these were free radical scavengers and antiexcitotoxic agents.

Neuroprotective agents aim to prevent neuronal death by inhibiting 1 or more of the pathophysiological steps in the processes that follow brain injury or ischemia due to occlusion of a cerebral artery. They also protect against neurodegeneration and neurotoxins. Application of new molecular technologies to dissect pathways and unravel mechanisms involved in damage to the nervous system are providing bases for development of new neuroprotective agents for diseases, which are currently treated by drugs that merely provide symptomatic relief. The concept of neuroprotection is now incorporated in development of drugs for neurologic disorders and more than 500 such approaches are in development.

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