Dr Antigoni Ekonomou
Wolfson Centre for Age Related Diseases

Endogenous Neurogenesis in the Human Brain

Purpose:  Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but little information exists for human studies. If the adult neural stem cells (ANSCS) that are normally present in the human brain do respond to a brain insult, it will be a very promising tool for brain regeneration with an improved clinical outcome, as it appears to be in experimental animal models. We therefore examined whether there was evidence of endogenous neurogenesis patients suffering from cerebrovascular diseseases.

Methods: We have defined a panel of antibodies that specifically label neural stem cells/neural progenitors in the adult human brain. Using immunohistochemistry on free floating vibratome sections, and paraffin-embedded sections, we examined the distribution of immunopositive cells around and distant from the infarcted area, and compared this to age-matched, healthy individuals. Furthermore, using immunohistochemistry, the position and level of neovascularisation was examined in correlation to the lesion and the endogenous neurogenesis.

Results: Interestingly, a large number of neural stem cells, Vascular Endothelial Growth Factor-immunopositive cells and new blood vessels were observed around the region of infarction, especially when the infarcts were recent, but not in other brain areas or in the same brain areas of the age-matched controls.  Furthermore, there was a 12-fold increase in the number of immunolabelled neural stem cells in the subventricular zone (SVZ), as well as many immunolabelled neural stem cells “en route” to the lesioned area. 

Conclusions: We report here the first evidence that increased endogenous neurogenesis originating from the SVZ is activated in cerebrovascular disease and is associated with neovascularisation in the region of cerebrovascular damage in adult human brain. Further studies will elucidate the mechanism of activation of this endogenous regenerative mechanism in the adult human brain, providing a very useful tool for therapeutic amplications.

This work was supported by the Alzheimer’s Research Trust (UK), The Medical Research Council (UK), and King’s College London