Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

Abstract

The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Specific Features of SVZ Neurogenesis After Cortical Ischemia: a Longitudinal Study

“…Our results indicate that cells that proliferate during the first week after ischemia (cells labeled at post-stroke days 1–7), despite successfully differentiating into neuroblasts and reaching the ischemic cortex, are not able to survive long term. This may be because the number of cells that proliferate at this time is lower and/or due to the ischemic environment at that time, still hostile due to the inflammatory processes activated after brain damage, impeding the integration process 41 . Although the possible direct functional benefit of this limited neurogenesis is doubtful, it is possible that these neuroblasts that reach the injured area contribute to the functional recovery through the contribution of trophic factors and/or other substances that help the remaining cells to solve the conflict in which they are.…”

Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington’s Disease

“…Induction of adult neurogenesis in response to many CNS trauma and neurological diseases has been reported by several studies in the past decade [ 184 , 185 ]. It has been demonstrated that ischemia is a well-known factor to contribute to reactive neurogenesis in the cortex [ 147 , 148 , 186 , 187 ]. The abnormal cortical neurogenesis has also been reported in multiple sclerosis [ 188 ] and ALS [ 189 ].…”

Mild hypothermia modulates the expression of nestin and caspase-3 in the sub-granular zone and improves neurological outcomes in rats with ischemic stroke

“…These neural stem/progenitor cells have the potential to survive brain ischemia and participate in neurogenesis after stroke [ 7 ]. The number of nestin-immunopositive cells (nestin + cells) is known to increase in the ischemic brain in response to focal cerebral ischemia/reperfusion injury [ 8 , 9 ]. However, while the effects of MH upon nestin + cells have been studied in neonatal cerebral hypoxic ischemic injury [ 10 - 13 ], as well as in adult global cerebral ischemia/reperfusion injury, which represents the clinical scenario of cardiac arrest [ 14 - 16 ], results have proved to be controversial and inconsistent.…”