The precursor
nerve growth factor (ProNGF) and its
receptor p75 neurotrophin receptor (p75NTR) are upregulated in several
brain diseases, including
ischemic stroke. The activation of p75NTR is associated with neuronal apoptosis and
inflammation. Thus, we hypothesized that p75NTR modulation attenuates brain damage and improves functional outcomes after
ischemic stroke. Two sets of experiments were performed. (1) Adult wild-type (WT) C57BL/6 J mice were subjected to intraluminal
suture-
middle cerebral artery occlusion (MCAO) to induce
cerebral ischemia. Pharmacological inhibitor of p75NTR,
LM11A-31 (50 mg/kg), or
normal saline was administered intraperitoneally (IP) 1 h post-MCAO, and animals survived for 24 h. (2) Adult p75NTR heterozygous knockout (p75NTR+/-) and WT were subjected to photothrombotic (pMCAO) to induce
ischemic stroke, and the animals survived for 72 h. The sensory-motor function of animals was measured using Catwalk XT. The brain samples were collected to assess
infarction volume,
edema, hemorrhagic transformation,
neuroinflammation, and signaling pathway at 24 and 72 h after the
stroke. The findings described that pharmacological inhibition and genetic knocking down of p75NTR reduce
infarction size,
edema, and hemorrhagic transformation following
ischemic stroke. Additionally, p75NTR modulation significantly decreased several anti-apoptosis markers and improved sensory motor function compared to the WT mice following
ischemic stroke. Our observations exhibit that the involvement of p75NTR in
ischemic stroke and modulation of p75NTR could improve the outcome of
ischemic stroke by increasing cell survival and enhancing motor performance.
LM11A-31 has the potential to be a promising therapeutic agent for
ischemic stroke. However, more evidence is needed to illuminate the efficacy of
LM11A-31 in
ischemic stroke.