Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study

Abstract

Background and purposeIntracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF).MethodsA rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA).ResultsIn the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume.ConclusionBDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling

“…However, the microenvironmental changes that occur after pathological damage typically impede neurogenesis and tissue repair ( Ge et al, 2023 ), resulting in neurological deficits. Previous studies have primarily focused on illustrating the changes in NSCs located in the SVZ during ICH ( Lin et al, 2023 ). However, these findings are insufficient in explaining the cognitive impairment following ICH.…”

Influence of Alcohol on Intracerebral Hemorrhage: From Oxidative Stress to Glial Cell Activation

“…After ICH, microglia and macrophages produce NTFs, particularly neurotrophins, to initiate repair. Studies have shown that BDNF can reduce hematoma volume, promote neural regeneration, and improve behavioral outcomes in models [ 129 , 130 , 131 , 132 ]. Similarly, NGF has been found to reduce inflammation and improve neurological function in patients [ 133 , 134 ].…”