Preterm infants have a high risk of neonatal white matter injury (WMI). WMI leads to reduced myelination, inflammation, and clinical neurodevelopmental deficits for which there are no effective treatments. Ionotropic glutamate receptor (iGluR) induced excitotoxicity contributes to oligodendrocyte (OL) lineage cell loss and demyelination in brain models of neonatal and adult WMI. Here, we hypothesized that simulated ischemia (oxygen‑glucose deprivation) damages white matter via activation of iGluR signaling, and that iGluR inhibition shortly after WMI could mitigate OL loss, enhance myelination, and suppress inflammation in an ex vivo cerebellar slice model of developing WMI. Inhibition of iGluR signaling by a combined block of AMPA and NMDA receptors, shortly after simulated ischemia, restored myelination, reduced apoptotic OLs, and enhanced OL precursor cell proliferation and maturation as well as upregulated expression of transcription factors regulating OL development and remyelination. Our findings demonstrate that iGluR inhibition post‑injury alleviates OL lineage cell loss and inflammation and promotes myelination upon developing WMI. The findings may help to develop therapeutic interventions for the WMI treatment.
Mohamed A. Al-Griw, Michael G. Salter, Ian C. Wood(1-2021)

The goal of this study was to investigate, in-vivo, the predominant mechanism of cell death, apoptosis versus necrosis, in the mature mouse brain exposed early to a ubiquitous environmental toxicant trichloroethane (TCE). A subset of male albino mice was injected intraperitoneally twice weekly for three weeks with TCE (100 and 400µg/kg). All animals were followed up for signs of toxicity and mortality. Changes in neural tissues were histpathologically evaluated. Biomarkers of brain cell number were also studied. The results showed that TCE insult triggered significant alterations in the microstructure of the brain tissues compared to controls. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates that cell apoptosis with necrosis was evident in the TCE-treated groups. The percent of necrosis was quantified as 20.09 ± 2.57% at 100µg/kg TCE, 30.57 ± 5.18% at 400µg/kg TCE, and 12.67 ± 1.25% in controls. However, the percent of apoptosis was quantified as 29.18 ± 1.51% at 100µg/kg TCE, 20.14 ± 2.12% at 400µg/kg TCE, and 8 ± 1.25% in controls. There was also a significant reduction in the brain DNA content in the TCE-treated groups. Agarose gel electrophoresis is also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation. These results correlated with neurobehavioral impairment. These findings indicate that TCE induces degeneration and apoptotic cell death in mouse brain, suggesting a crucial role played by apoptosis in TCE neurotoxicity.
Mohamed A. Al-Griw, Abdul Hakim Elnfati, Naser M. Salama, Massaud S. Maamar, Soad A. Treesh, Taher Shaibi(10-2015)

Exposure to trichloroethane (TCE), an industrial solvent, has been shown to be negatively associated with reproductive performance. The present study was performed to assess the effects of TCE exposure on the reproductive performance and outcome in mice during a critical developmental window of later reproductive life. A group of female mice were injected intraperitoneally twice weekly for three weeks with TCE (100 and 400 µg/kg). Mice were followed up for signs of toxicity and death. Changes in uterine tissues have also been investigated by histopathology. The results showed that TCE exposure has reduced the number of F0 fertile females comparing to controls. Moreover, TCE exposure resulted in a decreased pups number and changed sex ratio in the litter of F0 TCE­treated dams. Histopathological examination revealed a TCE­induced uterine toxicity appeared as a severe endometrial hyperplasia with squamous cell metaplasia and adenomyosis. These results indicate that TCE exposure during a critical reproductive developmental window could affect the fertility and interfere with the reproductive outcome in mice.
Mohamed A. Al-Griw, Seham A. Azreg, Emad M. Bennour, Salem A. El-Mahgiubi, Ali R. Al-Attar, Naser M. Salama, Abdul Hakim Elnfati(10-2015)