Strokes are devastating as there are no current therapies to prevent the long term neurological deficits that they cause. Soon after ischemic stroke, there is proliferation and differentiation of neural stem/progenitor cells as an important mechanism for neuronal restoration. However, endogenous neurogenesis by itself is insufficient for effective brain repair after stroke as most newborn neurons do not survive. One fascinating strategy for stroke treatment would thus be maintaining the survival and/or promoting the differentiation of endogenous neural stem/progenitor cells. Using transgenic (Tg) mice over-expressing the C. elegans fat-1 gene encoding an enzyme that converts endogenous omega-6 to omega-3 polyunsaturated fatty acids (n-3 PUFAs), we showed that fat-1 Tg mice with chronically elevated brain levels of n-3 PUFAs exhibited less brain damage and significantly improved long-term neurological performance compared to wild type littermates. Importantly, post-stroke neurogenesis occurred more robustly in fat-1 Tg mice after focal ischemia. This was manifested by enhanced neural stem cell proliferation/differentiation and increased migration of neuroblasts to the ischemic sites where neuroblasts matured into resident neurons. Moreover, these neurogenic effects were accompanied by significantly increased oligodendrogenesis. Our results suggest that n-3 PUFA supplementation is a potential neurogenic and oligodendrogenic treatment to naturally improve post-stroke brain repair and long-term functional recovery.

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The aim of this study was to evaluate the histological outcomes of chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (ALT) levels after long-term antiviral therapy. Paired liver biopsies before and after lamivudine (LAM) treatment in CHB patients with normal and elevated ALT levels were compared. Histological response was defined as a 1-point decrease according to the Scheuer scoring system, without worsening of fibrosis between pretreatment and posttreatment biopsies. Among the 48 patients who underwent paired liver biopsies, 17 had persistently normal baseline ALT level and 31 had elevated ALT level. The median age of the patients was 44 years and 72.9% of the patients were male. The median duration of antiviral treatment was 44.5 months (range 14-104). Long-term follow-up of liver biopsies revealed that 82.4% of patients in the normal ALT group and 61.3% in the elevated ALT group had a baseline fibrosis score of 4, which was reduced to 17.6% and 38.7% after long-term therapy, respectively, indicating reversal of cirrhosis in a large proportion of both groups, especially in patients with normal baseline ALT levels. Long-term antiviral treatment could achieve significant histological improvement in CHB patients with fibrosis or cirrhosis, regardless of ALT level.

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