Does inflammation after stroke affect the developing brain differently than adult brain?
The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative responses, is the major contributor to ischemic injury in both the immature and adult brain, but there are several areas where these responses diverge. We discuss the contribution of various inflammatory mechanisms to injury and repair after cerebral ischemia in the context of CNS immaturity. In particular, we discuss the role of lower expression of selectins, a more limited leukocyte transmigration, undeveloped complement pathways, a more rapid microglial activation, differences in cytokine and chemokine interplay, and a different threshold to oxidative stress in the immature brain. We also discuss differences in activation of intracellular pathways, especially nuclear factor kappaB and mitogen-activated protein kinases. Finally, we discuss emerging data on both the supportive and adverse roles of inflammation in plasticity and repair after stroke.
Vexler
Zinaida S
ZS
Department of Neurology, University of California, San Francisco, CA 94143-0663, USA. Zena.Vexler@ucsf.edu
Yenari
Midori A
MA
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000473:pathology*; D016923:Cell Death; D016207:Cytokines / Q000502:physiology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015398:Signal Transduction
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins