Lactate potentiates angiogenesis and neurogenesis in experimental intracerebral hemorrhage.

ABSTRACT: Lactate accumulation has been observed in the brain with intracerebral hemorrhage (ICH). However, the outcome of lactate accumulation has not been well characterized. Here, we report that lactate accumulation contributes to angiogenesis and neurogenesis in ICH. In the first set of the experiment,  a rat model of ICH was induced by injecting collagenase into the brain. The effects of lactate accumulation on the neurological function, apoptosis, and numbers of newborn endothelial cells and neurons, as well as the proliferation-associated signaling pathway, were evaluated in the rat brain.  In the second set, exogenous L-lactate was infused into intact rat brains so that its effects could be further assessed. Following ICH, lactate accumulated around the hematoma; the numbers of PCNA⁺/vWF⁺ nuclei and PCNA⁺/DCX⁺ cells were significantly increased compared with the numbers in the Sham group. Moreover, ICH induced translocation of nuclear factor-kappa B (NF-?B) p65 into the nucleus, resulting in a notable upregulation of VEGF and bFGF mRNAs and proteins compared with the levels in the Sham controls. Administration of a lactate dehydrogenase inhibitor dramatically inhibited these effects, decreased the vascular density, and aggravated neurological severity scores and apoptosis after ICH. After exogenous L-lactate infusion, the numbers of PCNA⁺/vWF⁺ nuclei and PCNA⁺/DCX⁺ cells were strikingly increased compared with the numbers in the Sham controls. In addition, lactate facilitated NF-?B translocation to induce increased transcription of VEGF and bFGF. Co-infusion with an NF-?B inhibitor significantly inhibited these effects. These data suggest that lactate potentiates angiogenesis and neurogenesis by activating the NF-?B signaling pathway following ICH.

SUBMITTER: Zhou J 

PROVIDER: S-EPMC6035243 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature