Loss of substance P and inflammation precede delayed neurodegeneration in the substantia nigra after cerebral ischemia
Brain, Behavior, and Immunity. 2013-03-01; 29: 51-61
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1. Brain Behav Immun. 2013 Mar;29:51-61. doi: 10.1016/j.bbi.2012.11.017. Epub 2012
Loss of substance P and inflammation precede delayed neurodegeneration in the
substantia nigra after cerebral ischemia.
Rodriguez-Grande B(1), Blackabey V, Gittens B, Pinteaux E, Denes A.
(1)Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester,
Focal cerebral ischemia leads to delayed neurodegeneration in remote brain
regions. The substantia nigra (SN) does not normally show primary neuronal death
after ischemic events affecting the striatum, but can exhibit delayed neuronal
loss after the ischemic injury through mechanisms that are unknown. No data are
available in mice showing acute post-stroke inflammation and remote injury in the
SN. Substance P (SP), a mediator of neurogenic inflammation, is a key element of
the striato-nigral circuitry, but alterations of SP in the SN have not been
studied after acute striatal injury. Inflammation, a key contributor to neuronal
death, is found in the SN after striatal ischemia, but it is unknown whether it
precedes or occurs concomitantly with neuronal death. We hypothesised that focal
striatal ischemia induces changes in SP levels in the SN and that inflammation
precedes neuronal death in the SN. Using the middle cerebral artery occlusion
model, we found a significant loss of SP in the ipsilateral SN 24h after striatal
ischemia in mice. In the same area where SP loss occurs, significant glial and
vascular activation, but no neuronal death, were observed. In contrast, a marked
neuronal loss was observed within six days in the area of SP loss and
inflammation. Our data suggest that focal loss of SP and early inflammatory
changes in the SN precede remote neuronal injury after striatal ischemic damage.
These observations may have important implications for motor impairment in stroke
patients and indicate that striatal ischemia might facilitate Parkinson’s disease
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 23232501 [Indexed for MEDLINE]