Effect of FK-506 on Inflammation and Behavioral Outcome Following Intracerebral Hemorrhage in Rat

Peeling, James; Yan, Hui-Jin; Corbett, Dale; Xue, Mengzhou; Bigio, Marc R. Del

doi:10.1006/exnr.2000.7564

Cited by 67 publications

(47 citation statements)

References 53 publications

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“…19,31,32,42,50 -54 Similar TUNEL-positive cells occur in subarachnoid hemorrhage models. 55 The TUNELpositive cells around ICH can be decreased by caspase inhibitors, 19 minocycline, 33 memantine, 56 FK506, 57 knockdown of tumor necrosis factor, 58 adenosine A2A activator CGS 21680, 59 tauroursodeoxycholic acid, 60 15d-prostaglandin J2 that activates PPAR␥, 54 and erythropoietin. 61 The current study adds to this list by showing that glutamate Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage

Ardizzone¹,

Zhan²,

Ander³

et al. 2007

Stroke

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Background and Purpose-The mechanisms by which intracerebral hemorrhages produce changes of blood flow and metabolism, cell death, and behavioral abnormalities are complex. In this study, we begin to test the hypothesis that intracerebral hemorrhage activates Src kinases that phosphorylate other molecules to produce cell injury and behavioral deficits after intracerebral hemorrhage (ICH). Methods-ICH was produced in adult Sprague Dawley rats by direct injection of autologous blood (50 L) into striatum.Src kinase activity, glucose hypermetabolic areas around the ICH, TUNEL-stained cells, and apomorphine-induced rotational behaviors were assessed in animals with ICH pretreated with the Src kinase inhibitor, PP1, or with vehicle. Results-PP1 (3 mg/kg) blocked increases of Src kinase activity (5-fold) at 3 hours after ICH. PP1 also blocked the areas of glucose hypermetabolism and decreased the numbers of TUNEL-stained cells surrounding the ICH at 24 hours. Finally, apomorphine-induced (1 mg/kg) rotation at 24 hours after ICH was markedly attenuated by previous treatment with PP1 (3 mg/kg intraperitoneal). Conclusions-PP1 decreases Src kinase activation, glucose metabolic activation, cell death, and behavioral abnormalities after ICH in striatum of adult rats. It is hypothesized that intracerebral hemorrhage, possibly via thrombin activation of protease-activated receptors, activates Src that phosphorylates NMDA receptors, matrix metalloproteinases, and other proteins that mediate injury after ICH.

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Section: Discussionmentioning

confidence: 99%

Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage

Ardizzone¹,

Zhan²,

Ander³

et al. 2007

Stroke

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“…Neurobehavioral testing was performed at days 3, 7, and 14 postimplantation. The behavioral tests included the ladder rung test and the cylinder test (7), and the total neurological deficit score (NDS) was obtained by summing the scores from all tests (48). In addition, the implanted animals were subjected to magnetic resonance imaging (MRI) examinations on a Bruker MSL-X Biospec 7T/21 MR system using a volume coil 2 cm in diameter.…”

Section: Methodsmentioning

confidence: 99%

West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence

Marle¹,

Antony

Ostermann

et al. 2007

J Virol

Self Cite

103

110

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West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1␤, and indolamine-2,3-deoxygenase with concurrent suppression of the protective astrocytespecific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNV C induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders.In North America, widespread West Nile virus (WNV) infection was first recognized in 1999 during an outbreak of viral encephalitis in New York City (32). Infection by WNV causes a spectrum of neurological disorders and ensuing death in a subset of infected individuals (24,26). WNV belongs to the flavivirus family (reviewed in references 11, 14, and 34), which are enveloped viruses with a genome consisting of one 10-to 11-kb single-stranded RNA molecule of positive-strand mRNA polarity. WNV genomic RNA contains one large open reading frame, which is translated into a single polypeptide and cleaved by viral and cellular proteases into three structural proteins and several nonstructural (NS) proteins (11, 34). The WNV structural proteins include the capsid (C) protein, the small transmembrane protein (M and its precursor preM), and the surface or envelope glycoprotein (E), which are all involved in pathogenesis. It is clear that infection of the centr...

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“…This widely-used model, developed by Rosenberg and colleagues (Rosenberg et al, 1993), consistently injures the striatum and results in a well-characterized profile of behavioral deficits that make it well suited to evaluating treatments (DeBow et al, 2003;MacLellan et al, 2006;Peeling et al, 2001). In Experiment 1, we quantified the volume of tissue lost at 7, 14 and 60 days after ICH using standardized histological procedures.…”

Section: Introductionmentioning

confidence: 99%

Progressive Brain Damage and Alterations in Dendritic Arborization after Collagenase-Induced Intracerebral Hemorrhage in Rats

Nguyen¹,

Huynh²,

Sjovold³

et al. 2008

CNR

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Intracerebral hemorrhage (ICH) was widely believed to be a monophasic event whereby cell death occurs from the initial space-occupying effects of the hematoma. However, we now know that secondary degenerative events contribute to delayed cell death, functional impairment and clinical deterioration. In three experiments, we further characterized the long-term maturation of injury in the collagenase model of striatal ICH in rat. First, we quantified the volume of tissue lost from 7 to 60 days showing that tissue loss more than doubled over this time. As the volume of tissue lost does not distinguish gray from white matter damage, gold chloride staining was used in a second experiment in ICH rats that survived 7 or 60 days. The mid-sagittal area of the corpus callosum significantly declined (22%) over this period, whereas the hippocampal and anterior commissures were not affected. A third experiment used the Golgi-Cox stain to examine dendritic arborization of peri-hematoma and contralateral medium spiny neurons of the striatum. We found an early and sustained increase in dendritic arborization in the non-lesioned hemisphere, whereas there was initial atrophy of peri-hematoma striatal neurons that eventually recovered to normal. These findings show that tissue loss, including white matter atrophy, continues over extended periods after ICH making it a potential target for cytoprotective agents. Finally, the dendritic alterations in both ipsi-and contralateral striatal neurons likely influence spontaneous recovery and are potential targets to further improve it.

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Effect of FK-506 on Inflammation and Behavioral Outcome Following Intracerebral Hemorrhage in Rat

Cited by 67 publications

References 53 publications

Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage

Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage

West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence

Progressive Brain Damage and Alterations in Dendritic Arborization after Collagenase-Induced Intracerebral Hemorrhage in Rats

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