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Published on: May 31, 2017
[Endogenous neuronal protection: an alternative approach]
1Departamento de Neurología Experimental, Instituto Nacional de Neurología y Neurocirugía, La Habana, Cuba. jorgedaniel.garcia@infomed.sld.cu
Introduction:
Despite a great number of neuroprotective agents have been evaluated successfully in experimental paradigms of brain ischemia and trauma, the results obtained in clinical trials in general do not satisfy the proposed criteria of efficacy. This fact leads to the searching of alternative approaches in order to orient the efforts towards neuronal protection with better perspectives.
Method:
By analyzing the brain tissue response after an ischemic insult we could observe that preconditioning with brief periods of ischemia produces tolerance, increasing the resistance against later lethal insults. Other stimuli, such as hypoxia and cortical spreading depression, induce similar responses. All of them, selectively induce specific genes, by acting collectively to increase the surviving potential of the nerve cells, promoting the functional recovery. Administration of some of these genes, or the proteins for which they codify--among them neurotrophic factors are remarkable examples--leads to interesting findings in the global and focal ischemia in rodents, which are mainly related to the inhibition of the ischemia-induced neuronal apoptosis.
Conclusion:
These findings also lead to think in an alternative approach for the neuronal protection, which take into consideration the brain endogen response as a promissory choice for a novel therapy.
Insights
Brain preconditioning with brief ischemia or hypoxia enhances neuronal resistance to injury. This endogenous response shows promise for novel neuroprotective therapies, improving functional recovery after ischemic events.
Area of Science:
- Neuroscience
- Cellular Biology
- Biomedical Research
Context:
- Clinical trials for neuroprotective agents often fail to meet efficacy criteria.
- Brain ischemia and trauma models show limited success in translating to human treatments.
- There is a need for alternative approaches to neuronal protection.
Purpose:
- To explore the potential of endogenous brain responses for neuroprotection.
- To investigate how preconditioning stimuli enhance neuronal resistance to injury.
- To identify therapeutic targets within the brain's natural defense mechanisms.
Summary:
- Preconditioning with brief ischemia, hypoxia, or cortical spreading depression induces tolerance and enhances neuronal resistance to lethal insults.
- These stimuli activate specific genes, increasing neuronal survival potential and promoting functional recovery.
- Administration of neurotrophic factors and other gene products inhibits ischemia-induced neuronal apoptosis in rodent models.
Impact:
- Findings suggest that leveraging the brain's endogenous response is a promising strategy for novel neuroprotective therapies.
- This approach could lead to more effective treatments for conditions like stroke and traumatic brain injury.
- Focusing on intrinsic cellular mechanisms may overcome limitations of current neuroprotective drug development.
