Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats.
Polyamines (putrescine, spermidine and spermine) are ubiquitous cellular components, but their specific role in central nervous system (CNS) injury has yet to be characterized. CNS injury results in increased activities of ornithine decarboxylase and spermidine/spermine-N(1)-acetyltransferase, and accumulation of putrescine. The present study determined the polyamine profile in three models of CNS injury, in two different species (gerbil and rat) and two strains of rats (Sprague-Dawley and spontaneously hypertensive): (1) transient focal cerebral ischemia in spontaneously hypertensive rats (SHR); (2) traumatic brain injury in Sprague-Dawley rats; and (3) transient forebrain ischemia in gerbils. While there was a significant increase in putrescine in all three models, spermine and spermidine levels were unaltered in forebrain ischemia and traumatic brain injury. However, transient focal cerebral ischemia shows depletion of spermine and spermidine levels in injured hemisphere compared to contralateral region. Exogenous spermine significantly restored the spermine as well as spermidine levels in the ipsilateral hemisphere after transient focal cerebral ischemia, but did not alter putrescine levels or the ratio of spermidine to spermine. The loss of spermine in particular, may have several consequences that contribute to ischemic injury, including destabilization of chromatin, decreased mitochondrial Ca(2+) buffering capacity, and increased susceptibility to oxidative stress. Based on our and other studies, we propose a tentative antioxidant mechanism of spermine neuroprotection.
Adibhatla
Rao Muralikrishna
RM
Department of Neurological Surgery, H4-330, Clinical Science Center, 600 Highland Avenue, University of Wisconsin-Madison, Madison, WI 53792-3232, USA. adibhatl@neurosurg.wisc.edu
Hatcher
James F
JF
Sailor
Kurt
K
Dempsey
Robert J
RJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*
D013096:Spermine; D013095:Spermidine; D011700:Putrescine