Dr. Rao M. Adibhatla, Research Professor
Start–Up Funding from University of Wisconsin
University of Wisconsin Med. School Research
Mechanisms of CDP–choline (citocoline) neuroprotection in cerebral ischemia.
Citocoline is thought to improve the outcome of patients in phase III clinical trials of stroke. It has shown to have beneficial effects in a number of CNS injury models. Although experimental evidence is limited, the therapeutic action of citocoline is thought to be due to stimulation of phosphatidylcholine (PtdCho) synthesis in a damaged brain. Understanding the actions of citocoline could lead to development of more efficient treatment strategies for ischemia / reperfusion injury. Our studies of transient cerebral ischemia suggest that citocoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin. Citocoline could also act by inhibiting destructive processes (activation of phospholipases). The major mechanism of action of citocoline may be in modulating activation of phospholipase A2.
Polyamines in cerebral ischemia.
Polyamines (putrescine, spermidine and spermine) are ubiquitous cellular components. The role of alterations in polyamine metabolism in neuronal degeneration after CNS injury remains an unresolved issue. Polyamines are important in the stabilization of cellular components such as cell membranes and chromatin structures; depletion of polyamines could lead to loss of cell integrity and cell death. Transient cerebral ischemia results in loss of spermine and spermidine. Our research seeks to determine whether normalization of the transient, ischemia–induced polyamine imbalance is neuroprotective. Spermine is considered to be an antioxidant and free radical scavenger, and restoring its levels may protect the brain from oxidative damage (either by scavenging hydroxyl radical or chelating Fe2+) following ischemia / reperfusion.
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|Citicoline and Lipids|
Adibhatla RM and Hatcher JF (2003). Citcoline attenuates phospholipase A2 stimulation and hydroxyl radical generation after transient cerebral ischemia. J. Neurosci. Res. (in press).
Adibhatla RM, Hatcher JF and Dempsey RJ (2003). Phospholipase A2, hydroxyl radicals and lipid peroxidation in transient cerebral ischemia. Antiox. Redox Signal. (in press).
Kirkland RA, ADIBHATLA RM, Hatcher JF, Franklin JL (2002): Loss of cardiolipin and mitochondria during programmed neuronal death: Evidence of a role for lipid peroxidation and autophagy. Neuroscience.
ADIBHATLA RM, Hatcher JF (2002): Citicoline mechanisms and clinical efficacy in cerebral ischemia. Journal of Neuroscience Research.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2002): Citicoline: Neuroprotective mechanisms in cerebral ischemia. Journal of Neurochemistry.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2002): Citicoline: Mechanisms and stroke clinical trials. Neurology..
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2001): Does choline modulate phospholipase activities after transient forebrain ischemia? Brain Research.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2001): Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2000): Lipid alterations in transient forebrain ischemia: Possible new mechanisms of choline neuroprotection. Journal of Neurochemistry.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (2000): Neuroprotection by group I metabotropic glutamate receptor antagonists in forebrain ischemia of gerbil. Neuroscience Letters.
Baskaya MK, Dogan A, ADIBHATLA RM, Dempsey RJ (2000): Neuroprotective effects of choline on brain edema and BBB breakdown after TBI. Journal of Neurosurgery.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): Lipid metabolism in ischemic neuronal death. Recent Research Developments in Neurochemistry.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): CDP–choline: Neuroprotection in transient forebrain ischemia of gerbils. Journal of Neuroscience Research.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): Arachidonic acid and leukotriene C4: Role in transient cerebral ischemia of gerbils. Neurochemistry Research.
ADIBHATLA RM, Hatcher JF, Sailor K, Dempsey RJ (2002): Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Research.
ADIBHATLA RM, Hatcher JF, Dogan A, Dempsey RJ (2000): Elevated N1—acetylspermidine levels in gerbil and rat brains after CNS injury. Journal of Neurochemistry 74:1106—1111.
ADIBHATLA RM, Hatcher JF, Vemuganti LRR, Baskaya MK, Dempsey RJ (1999): Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion. Journal of Neurochemistry 72:765—770.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): The contribution of polyamine oxidase to brain injury after trauma. Journal of Neurosurgery 90:1078—1082.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): The role of the polyamine inter conversion pathway on edema, ischemic injury volume and polyamine levels in rats after temporary MCAO. Journal of Neurochemistry 72:765—770.
ADIBHATLA RM, Hatcher JF, Dempsey RJ (1999): Polyamine response to CNS injury: For better or for worse? Recent Research Developments in Neurochemistry 2:517—532.
ADIBHATLA RM, Hatcher JF, Baskaya MK, Dempsey RJ (1998): Simultaneous assay of ornithine decarboxylase and polyamines after central nervous system injury in gerbil and rat. Neuroscience Letters 256:65—68.
Vemuganti LRR, Baskaya MK, ADIBHATLA RM, Dogan A, Dempsey RJ (1998): Increased ornithine decarboxylase activity and protein level in the cortex following traumatic brain injury in rats. Brain Research 783:163—166.
Baskaya MK, ADIBHATLA RM, Dogan A, Donaldson D, Gellin G, Dempsey RJ (1997): Regional brain polyamine levels in permanent focal cerebral ischemia. Brain Research 744:302—308.
ADIBHATLA RM, Baskaya MK, Maley ME, Kindy MS, Dempsey RJ (1997): Beneficial effects of Shttps://www.angelfire.com/wizard/www.mani.com/rao/raolabs.htmladenosyl—methionine on blood–brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. Molecular Brain Research 44:134—138.
Baskaya MK, ADIBHATLA RM, Dogan A, Donaldson D, Dempsey RJ (1997): The biphasic opening of the blood–brain barrier in the cortex and hippocampus after traumatic brain injury in rats. Neuroscience Letters 226:33—;36.
Vemuganti LRR, Bowen KK, ADIBHATLA RM, Dempsey RJ (2001): Up—regulation of the peripheral—type benzodiazepine receptor expression and [3H]PK11195 binding in gerbil hippocampus after transient forebrain ischemia. Journal of Neuroscience Research 64:493—500.
ADIBHATLA RM, Dogan A, Hatcher JF, Dempsey RJ (1998): Fluorometric assay of nitrite and nitrate in brain tissue after traumatic brain injury and cerebral ischemia. Brain Research 793:265—270.
Editor and Publisher: Nagamani Adibhatla
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Last update: April 28, 2003