Cannabinoid rescue of striatal progenitor cells in chronic Borna disease viral encephalitis in rats.
ABSTRACT A growing number of environmental and pharmacologic manipulations have been shown to influence adult neurogenesis. Borna disease virus (BDV) in rats causes cortical and subcortical infection with extrapyramidal motor symptoms, and hippocampal infection suppresses neurogenesis. Given the known effects of cannabinoids in promoting neural progenitor cell survival, the authors examined in vivo effects of chronic BDV infection in rats on BrdU-positive progenitor cells in striatum, together with neuroprotective actions of cannabinoids. Birth and survival of BrdU-positive progenitor cells in striatum of BDV-infected rats treated with a general cannabinoid agonist (WIN 55,212 1 mg/kg i.p. b.i.d. x 7 days) were examined, as well as anti-inflammatory, antiviral, and nutritional effects of cannabinoids. Cannabinoid treatment protected BrdU-positive progenitor cells in striatum that were susceptible to virus-induced injury (p < .01) through suppression of microglia activation (p < .001). As a consequence of their anti-inflammatory actions and support of neural progenitor cell survival, cannabinoids may be adjunctive treatment for encephalitides with microglial inflammation and neurodegeneration.
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ABSTRACT: Cranial radiation therapy causes a progressive decline in cognitive function that is linked to impaired neurogenesis. Chronic inflammation accompanies radiation injury, suggesting that inflammatory processes may contribute to neural stem cell dysfunction. Here, we show that neuroinflammation alone inhibits neurogenesis and that inflammatory blockade with indomethacin, a common nonsteroidal anti-inflammatory drug, restores neurogenesis after endotoxin-induced inflammation and augments neurogenesis after cranial irradiation.Science 01/2004; 302(5651):1760-5. · 31.20 Impact Factor
Article: Cannabinoids and neuroinflammation.[show abstract] [hide abstract]
ABSTRACT: Growing evidence suggests that a major physiological function of the cannabinoid signaling system is to modulate neuroinflammation. This review discusses the anti-inflammatory properties of cannabinoid compounds at molecular, cellular and whole animal levels, first by examining the evidence for anti-inflammatory effects of cannabinoids obtained using in vivo animal models of clinical neuroinflammatory conditions, specifically rodent models of multiple sclerosis, and second by describing the endogenous cannabinoid (endocannabinoid) system components in immune cells. Our aim is to identify immune functions modulated by cannabinoids that could account for their anti-inflammatory effects in these animal models.British Journal of Pharmacology 04/2004; 141(5):775-85. · 5.07 Impact Factor
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ABSTRACT: Neonatal Borna disease virus (BDV) infection of the rat brain serves as a valuable model for studying the pathogenesis of neurodevelopmental abnormalities following early brain injury. Previous experiments have demonstrated significant alterations in regional tissue content of serotonin (5-HT) in neonatally BDV-infected Lewis rats. The present study sought to provide more insights into postnatal virus-associated alterations in 5-HT neurotransmission by evaluating the density of 5-HT1a receptors in the hippocampus and 5-HT2a receptors in the cortex, regional 5-HT tissue concentrations, behavioral responses to a 5-HT agonist, quipazine, and numbers of neurons in specific subfields of the hippocampus on days 7, 14, and 30 after neonatal BDV infection in Lewis rats. Neonatal BDV infection was found to be associated with a gradual increase in the density of 5-HT2a and 5-HT1a postsynaptic receptors followed by an elevation of 5-HT contents at both the levels of synaptic terminals (i.e., cortex and hippocampus) and cell bodies (i.e., raphe nuclei). In addition, there was an enhanced behavioral response to quipazine. Virus-associated neurochemical and behavioral changes were accompanied by a decline in the number of neurons in the dentate gyrus and in the CA1 field of the hippocampus. No change in the number of neurons in the CA3/2 field of the hippocampus was observed. The present pattern of BDV-associated alterations in 5-HT brain system along with available data from other laboratories suggest that BDV might compromise axonal transport and/or release of 5-HT, resulting in decreased 5-HT neurotransmission.Journal of NeuroVirology 11/2004; 10(5):267-77. · 2.85 Impact Factor