Year: 2011
Type: article
Abstract: T he approach to neuroprotection in stroke has relied mainly on exogenously administered drugs derived from research probing the cellular mechanisms of ischemic brain injury.This approach has had limited translational impact.Over 1000 putative neuroprotective agents have been developed, and over 100 agents have advanced to clinical trials.None, however, have shown clinical efficacy. 1y contrast, a gene-based approach seeks to harness endogenous neuroprotective programs for stroke therapy.Experimentally, ischemic brain injury can be attenuated, and stroke outcome improved, by gene expression modification in the brain.The brain and other organs have highly conserved, endogenous neuroprotective programs, the induction of which reduces ischemic injury.The neuroprotective programs can be induced in the model of ischemic tolerance: brief exposure to sublethal ischemia produces tolerance to a subsequent, severe ischemic challenge.3][4][5] The protection induced by tolerance is substantial, gene-based, and dependent on new protein synthesis.The neuroprotection of tolerance has been demonstrated in experimental cardiopulmonary bypass surgery 6 and in stroke in the primate. 7A clinical counterpart likely exists in human brain: patients with prodromal transient ischemic attacks have milder strokes. 8 -11 Two small clinical trials have shown potential benefits of preconditioning, and 5 additional trials are underway. 12Thus, there is considerable therapeutic potential in understanding gene expression changes in tolerance and in dissecting the biological mechanisms that regulate them.This is an evolving story deriving mainly from the authors' and our collaborators' laboratories.
Source: Stroke
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Rapid ischemic tolerance: Synaptic re-organization and reduced excitotoxicity, Morehouse School of Medicine Center of Excellence Research Endowment Program, Molecular mechanisms of seizure induced brain injury, Morehouse School of Medicine G12 Multidisciplinary Biomedical Research Center, Molecular Mechanisms of Ischemia, Brain ischemia attenuates neuropeptide biosynthesis, RCMI Infrastructure for Clinical and Translational Research (RCTR) (U54), RCMI Infrastructure for Clinical and Translational Research (RCTR) (U54)
OpenAlex ID: W1978111954