The neuroprotective roles of BDNF in hypoxic ischemic brain injury

Abstract

Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury.

Keywords: brain injury; brain-derived neurotrophic factor; hypoxic; ischemia.

Figure 1

Possible mechanisms of brain-derived neurotrophic factor (BDNF) in neuronal survival after hypoxia-ischemia (H/I). Pro-BDNF selectively activates p75 receptor, thereby inducing pro-apoptotic signalling pathways (25). Mature BDNF binds with kinase receptor type B (TrkB), exhibiting a positive effect in two ways, i.e., one side promotes neural regeneration and rehabilitation of cognition and memory, while the other side is against the pathological process of inflammation, neurotoxicity, periventricular leukomalacia, epilepsy and apoptosis.