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

Abstract

The present study was conducted to clarify whether treatment with L-serine can improve the brain repair and neurorestoration of rats after permanent middle cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin-C, and Nogo-A levels were measured. Proliferation and differentiation of the neural stem cells (NSCs) and proliferation of the microvessels in the ischemic boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days or until the end of the experiment. L-Serine treatment: 1) reduced the lesion volume and neuronal loss; 2) improved the recovery of neurological functions; 3) elevated the expression of nerve growth-related factors; and 4) facilitated the proliferation of endogenous NSCs and microvessels activated after pMCAO and increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of serine hydroxymethyltransferase, blunted the effects of L-serine on NSC proliferation, differentiation, microvascular proliferation. In conclusions, L-serine treatment in pMCAO rats can reduce brain injury and facilitate neurorestoration which is partly associated with the improvement of proliferation of NSCs and microvessels, reconstruction of neurovascular units and resultant neurorepair. The effects of L-serine on endogenous NSC proliferation and microvascular proliferation are partly mediated by the action of L-serine as a substrate for the production of one-carbon groups used for purine and pyrimidine synthesis and modulation of the expression of some nerve growth-related factors.

Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner

“…Rats scoring 0, 1, 4 points were excluded from the experiment. Rotarod motor tests 54 55 and Modified Neurological Severity Scores (mNSS) 14 56 57 were performed to evaluate neurological function 1 day before and 1, 3, 7 days after MCAo. The mNSS included tests of motor, sensory, reflex and balance performance with scores ranging from 0 (normal) to 18 (maximal deficit).…”

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

“…found that L‐serine infusion reduced the infarct volume in a mouse MCAO model, and they speculated that this action of L‐serine may be dependent on a vasodilatory effect, since L‐serine increases cerebral blood flow . Furthermore, a neuro‐restorative role of L‐serine, in addition to its neuroprotective role, has been postulated …”

“…163 Furthermore, a neuro-restorative role of L-serine, in addition to its neuroprotective role, has been postulated. 164…”

Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

“…L-serine is a non-essential amino acid that exhibits essential functions in the central nervous system, particularly protein synthesis and cell proliferation [28]. For example, treatment with L-serine facilitated the proliferation of NSCs derived from rats with induced brain injury, and pharmacological inhibition of the enzyme serine hydroxymethyltransferase (SHMT) impaired the effects of L-serine on NSC proliferation [29]. SHMT initiates L-serine catabolism in the one-carbon metabolism for purine and pyrimidine synthesis [28], suggesting that L-serine possibly acts on NSPCs through this pathway.…”