The neuroprotective effect of N-acetylcysteine and therapeutic effect of bone marrow-derived mesenchymal stromal cells on locus coeruleus in a rat model of cuprizone-induced central nervous system demyelination: behavioral and histological study

Cuprizone (CPZ) is widely used experimentally to induce CNS toxic injury accompanied by oxidative stress, mitochondrial dysfunction and demyelination. The locus coeruleus (LC), a predominantly unmyelinated or sparsely myelinated noradrenergic nucleus, may be vulnerable to such metabolic and oxidative insults. N-acetylcysteine (NAC) has antioxidant and neuroprotective properties, whereas bone marrow-derived mesenchymal stromal cells (BM-MSCs) have potential regenerative and neuroprotective effects. The purpose of this work was to study the neuroprotective effect of NAC and therapeutic effect of bone marrow-derived mesenchymal stromal cells on cuprizone-induced injury of the locus coeruleus in adult male albino rats using behavioral, histological, immunohistochemical and ultrastructural assessments. Forty-five male adult albino rats were divided into; Group I: control; Group II: cuprizone treated; Group III: cuprizone and N-acetylcysteine; Group IV: cuprizone treated then 24 hours later, rats received a single intravenous injection of 1×106 bone marrow-derived mesenchymal stromal cells into rat tail vein and were left for another 10 days. Finally, behavioral, statistical, light and electron microscopic tissues were evaluated for locus coeruleus (LC). Group II of LC showed highly significant changes in different behavioral tests and affected noradrenergic neurons seen by H&E, toluidine blue and cresyl violet stains. Also, significant immunohistochemical findings regarding anti-tyrosine hydroxylase, anti-glial fibrillary acidic protein and anti-caspase-3. Besides, marked electron microscopic findings regarding cell organelles. Group III and IV of LC showed mild and marked improvement of the previously mentioned findings, respectively. N-acetylcysteine and stromal cells had a significant neuroprotective and ameliorative effect on histopathological changes of LC induced by cuprizone.Cuprizone, locus coeruleus, mesenchymal stromal cells, N-acetylcysteine, PKH26.