Expression of Brain-Derived Neurotrophic Factor (BDNF) Increases the Resistance of Neurons to Death in the Postresuscitation Period

A search for substances that are able to protect brain cells from the damaging effect of hypoxia remains one of the most relevant issues in modern neurobiology and medicine. Whether neurotrophic factors, brain-derived neurotrophic factor (BDNF) protein in particular, can be used to treat neurological diseases is the subject of wide speculation in the literature now. However, how the expression of this protein in the brain neurons changes after systemic circulatory arrest in the postresuscitation period remains uncertain.

Objective: to estimate the level of BDNF expression in the highly ischemia-sensitive neuronal population of cerebellar Purkinje cells and the value of BDNF in the resistance of neurons to ischemia-reperfusion.

Materials and methods. In mature outbred male albino rats (n=11), the heart was stopped under ether anesthesia at 12 minutes via intrathoracic ligation of the vascular fascicle, followed by revivification. A control group included pseudo-operated animals (n=11). On days 7 after revivification, a morphometric analysis of Nissl-stained paraffin sections 5—6 μm thick was used to determine the total number of Purkinje cells per 1 mm of their layer length. The expression of BDNF protein in the Purkinje cells was immunohistochemically examined by an indirect peroxidase-antiperoxidase test using primary polyclonal antibodies against BDNF. The count of Purkinje cells with different immune responses to BDNF protein was calculated. The intensity of BDNF expression was estimated from the mean optical density. Results. 12-minute systemic circulatory arrest in the rats resulted in a 12.5% reduction in the number of Purkinje cells. The immunohistochemical examination revealed a lower numbers of BDNF– neurons in the resuscitated rats. In this case, the count of BDNF+ and BDNF++ neurons corresponded to their reference level. Consequently, only BDNF-negative neurons, i.e. those that failed to express BDNF protein, died. Analysis of the mean optical density indicated that the remaining neurons had a higher BDNF protein expression than those in the controls. The found facts suggest that this protein has a neuroprotective effect in the postresuscitation period.

Conclusion. The capability for BDNF expression is an important factor that enhances neuronal resistance to death in the postresuscitation period. This offers promise for BDNF use to elaborate novel approaches to protecting the brain in ischemia-reperfusion.

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