The role of BDNF signaling in hypoxia-induced apoptosis in cultured cortical networks.

In the core of a stroke, cell death occurs within minutes. In the penumbra, activity quickly drops, but cells typically remain viable for several hours. Improving neuronal survival in the penumbra is crucial for enhancing recovery in patients with stroke. Earlier work showed that mild activation may improve recovery, but the mechanisms are unclear. Brain-derived neurotrophic factor (BDNF) is well recognized for its neuroprotective functions via activation of tyrosine receptor kinase B (TrkB) receptors, and its release is activity-dependent. This study explored the role of BDNF/TrkB signaling in neuronal survival under hypoxic conditions, using cultures of dissociated cortical rat neurons. When exposed to hypoxia, activity quickly drops and cells become apoptotic after ∼12 h, similar to observations in the ischemic penumbra. Inhibition of the TrkB receptor in healthy, normoxic cultures led to a fivefold increase in apoptosis, confirming the importance of BDNF/TrkB signaling for cell viability in these preparations. The addition of BDNF to hypoxic cultures significantly improved neuronal survival, comparable with the effects of mild activation. These findings suggest that the beneficial effect of mild stimulation to prevent apoptosis in hypoxic cultures is mediated by BDNF/TrkB signaling, offering insights for potential therapeutic strategies aimed at promoting neuronal recovery after a stroke.NEW & NOTEWORTHY Low activity in the ischemic penumbra has been suggested as a critical factor leading to apoptosis. BDNF excretion is activity-dependent and has been shown to be neuroprotective. Blockade of TrkB receptors induced apoptosis in cultured neurons, comparable with the effects of hypoxia. BDNF administration was effective in mitigating hypoxia-induced apoptosis, suggesting that the beneficial effect of mild activation to prevent apoptosis in hypoxic cultures is mediated by BDNF-TrkB signaling.