Improvement in Regional CBF by L-Serine Contributes to Its Neuroprotective Effect in Rats after Focal Cerebral Ischemia

Abstract

To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF). Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1) reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2) improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3) increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca2+-activated K+ channels on the cerebral blood vessel endothelium.

L-Serine Treatment May Improve Neurorestoration of Rats after Permanent Focal Cerebral Ischemia Potentially Through Improvement of Neurorepair

“…These results are consistent with our previous observations on the therapeutic effect of L-serine in transient and permanent cerebral ischemic rats [21], [22]. The present study extended the observation time to 35 days after cerebral ischemia and more parameters, especially the learning and memory that were used to evaluate the recovery of neurological functions in rat.…”

“…These are novel mechanisms underlying the therapeutic effect of L-serine for the rats with ischemic brain injury, in addition to the glycine receptor-mediated neuroprotective mechanism and the endothelial apamin- and charybdotoxin-sensitive Ca 2+ -activated K + channels-mediated vasodilation mechanism we reported previously [21], [22]. Thereby, combining with present results we reported here, we suggest that L-serine might be a new candidate for the treatment of ischemic brain injury because of its actions on multiple targets.…”

Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson's disease

“…L‐serine is a crucial neurotrophic factor in the CNS as it is a precursor for nucleotides, neurotransmitters, sphingolipids, phosphatidylserine, and L‐cysteine (Ren et al . ). Moreover, the increased levels of neuronal‐specific ENO2 and 3‐PGDH are likely a cellular stress response to prevent cell death in the absence of PINK1 (presence of mitochondrial dysfunction), consistent with the finding that blocking glycolysis in PINK1‐deficient mouse embryonic fibroblasts led to rapid death of these cells (Akundi et al .…”

Does the application of Opsite⋄ Flexigrid⋄ occlude the oxygen saturation readings in healthy individuals using the moorVMS‐OXY machine?

“…To conclude, there are very few MoorVMS-OXY studies done on humans, but from the literature found, it is used widely showing it is reliable and clinically applicable [26][27][28][29][30][31][32]. Oxygen is vital to ensure wound healing, and a lack of oxygen can delay the healing process [2].…”