Ischaemic injury during brain development correlates with long-term neurological problems resulting in part from oligodendrocytes (OL) damage and a loss of appropriate myelination. The molecular and cellular mechanisms responsible remain partially understood and there is no effective clinical treatment. Here we develop and characterise an ex-vivo slice culture ischaemia model to elucidate the cellular mechanisms to aid the search for therapeutic interventions. Cerebellar slices from 7 day-old rats were cultured for 10 days and their developmental profile in culture and their response to oxygen-glucose deprivation (OGD) was assessed. During the culture period development of white matter progressed as in-vivo, the numbers of oligodendrocyte precursor cells (OPC) decreased and the numbers of mature OLs increased and there was extensive myelination of axons as judged by colocalisation of myelin basic protein and neurofilament. Cultured slices were exposed to a short period of OGD at 7 days in-vitro and reperfused to mimic in-vivo conditions. Twenty minutes of OGD was found to result in significant injury as judged by a 58.6% reduction in cell viability 3 days post-injury. Treatment of cultures with OGD resulted in a loss of OLs and a loss of myelination of axons. In summary we have developed a paradigm for studying the damage to OLs and loss of myelination associated with ischaemic periods during development which should facilitate the search for understanding the mechanisms responsible and identifying potential therapeutic interventions.
Mohamed A M Al Griw , Mohamed A. Al-Griw, Ian C. Wood, Michael G. Salter(11-2017)

Alterations in genes encoding the xenobiotic-metabolizing enzymes contribute to the variability in susceptibility to various cancers. In this study, we assessed the possible association between the CYP1A1 variants and lung cancer (LC) risk in a population of Libyan males. For this study, we selected 20 unrelated healthy controls and 32 patients with LC. DNA samples from the controls and patients were screened by DNA-PCR and direct DNA sequence analysis to search for genetic sequence variations in CYP1A1 gene (exon 7 and 3’ non-coding region). CYP1A1 mutations were identified in 11.5 % adult subjects and cases analyzed, and all were males. Overall, 11 CYP1A1 mutations were documented in this study implicating exon 7 and 3’ non-coding region. Nonsense, missense, and frame-shift mutations accounted for, respectively, 27.3 %, 63.6 % and 9.1 % of all CYP1A1 mutations. Three missense mutations namely CYP1A1*2B/m2 (rs1048943), CYP1A1*4/m4 (rs1799814), and CYP1A1*2A/m1 (rs4646903) have already been reported. The remaining mutations have not been described previously. We observed two apparently heterozygous carriers of mutation CYP1A1*2B/m2 (CYP1A1 4889A/G [642Ile/Val] genotype) in control group. We also observed two heterozygotic genotypes one containing mutation m4 (CYP1A1 4887C/A [461Thr/Asp]) and another containing mutation m1 (6235T/C) in cancer group. The mutations m2, m4, and m1 accounted for, respectively, 18.2 %, 9.1 % and 9.1 % of all CYP1A1 mutations. Comparing the clinical features showed that PLT and WBC counts were lower in CYP1A1 mutant than in CYP1A1 wild type, but they have not reached statistical significant (P > 0.05). The average age of CYP1A1 mutant was lower than in CYP1A1 wild type. Overall, these findings suggest that genetic alterations in the metabolic gene CYP1A1 are too rare to be of clinical relevance in this study, implying different pathways for the LC risk with respect to CYP1A1 polymorphisms as a risk factor for LC at least in this study.
Najah A. Fares, Othman A. El-Ansari, Mohamed A. Al-Griw(4-2017)

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)