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N-acetyl cysteine (NAC) is a glutathione precursor with reported antioxidant and neuroprotective potentials. Recent therapy for combating AD is known to provide only symptomatic relief thus necessitating the discovery of new drugs and their mechanism of action. This study was aimed to demonstrate the in vivo neuroprotective effect of NAC against aluminum (Al<jats:sup>3+<\/jats:sup>)-induced neuro-degeneration in rats (a model for AD). Twenty- five (25) adult male Wistar rats used for this study were divided into 5 groups: Group A\u2009=\u2009Control, B\u2009=\u2009Aluminum chloride (200\u00a0mg\/kg), C\u2009=\u20091000\u00a0mg\/kg of NAC\u2009+\u2009Aluminum chloride (200\u00a0mg\/kg), D\u2009=\u20091000\u00a0mg\/kg of NAC, E\u2009=\u2009Aluminum chloride (200\u00a0mg\/kg) was orally\u00a0administered daily for 3\u00a0weeks and discontinued for one week. Frontal Cortex harvested for histological analysis using Haematoxylin and Eosin stain, Cresyl Fast Violet stain for Nissl granules and Glial fibrillary acidic protein\u00a0immunohistochemistry specific for astrocytes. Aluminum significantly induced oxidative stress, coupled with marked neurons necrosis, chromatolysis and gliosis in the frontal cortex, upon NAC administration, there was neuro anti-inflammatory response as seen in the significant reduction in astrocytes expression, neuronal cell death and Nissl body aggregation which attenuates neuropathological deficits induced by Al<jats:sup>3+<\/jats:sup>. It was shown that aluminum is a neurotoxin mediating AD-like oxidative stress, NAC has a therapeutic potential associated with its potent in vivo interaction with astrocytes in response to Al<jats:sup>3+<\/jats:sup> neuro-inflammation seen in positive expression of Nissl granules and glial cells in addition to possibility of endogenous glutathione neuroprotection after withdrawal of stress mediator in neurodegeneration.<\/jats:p>","DOI":"10.1007\/s11011-020-00556-9","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:02:45Z","timestamp":1585054965000},"page":"829-839","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Histomorphological evaluations on the frontal cortex extrapyramidal cell layer following administration of N-Acetyl cysteine in aluminum induced neurodegeneration rat model"],"prefix":"10.1007","volume":"35","author":[{"given":"Memudu Adejoke","family":"Elizabeth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantong","family":"Samson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osahon Roli","family":"Itohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"556_CR1","unstructured":"Abbasali KM, Zhila T, Farshad N (2005) Developmental toxicity of aluminum from high doses of AlCl3 in mice. 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