Induction of Tumor Necrosis Factor-<i>α</i> in the Mouse Hippocampus following Transient Forebrain Ischemia

Uno, Hisakazu; Matsuyama, Tomohiro; Akita, Hiroshi; Nishimura, Hiroyuki; Sugita, Minoru

doi:10.1097/00004647-199705000-00002

Cited by 155 publications

(80 citation statements)

References 40 publications

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“…We tested the ability of Slit to modulate chemotaxis in the in vivo brain using two different proinflammatory stimuli: The cytokine TNFα (Carvalho-Tavares et al, 2000), and transient global ischemia, in which TNFα derived from resident cells (Liu et al, 1994;Gregersen et al, 2000;Botchkina et al, 1997;Uno et al, 1997;Feuerstein et al, 1998) and mediators of other inflammatory signaling cascades promote postischemic inflammation in the postcapillary venular system and in cerebral parenchyma. In both models, we found exogenously administered Slit to be potently effective in reducing cerebrovascular inflammation.…”

Section: Discussionmentioning

confidence: 99%

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Altay

McLaughlin

et al. 2007

Experimental Neurology

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Cerebrovascular inflammation contributes to secondary brain injury following ischemia. Recent in vitro studies of cell migration and molecular guidance mechanisms have indicated that the Slit family of secreted proteins can exert repellant effects on leukocyte recruitment in response to chemoattractants. Utilizing intravital microscopy, we addressed the role of Slit in modulating leukocyte dynamics in the mouse cortical venular microcirculation in vivo following TNFα application or global cerebral ischemia. We also studied whether Slit affected neuronal survival in the mouse global ischemia model as well as in mixed neuronal-glial cultures subjected to oxygenglucose deprivation. We found that systemically administered Slit significantly attenuated cerebral microvessel leukocyte-endothelial adherence occurring 4 h after TNFα and 24 h after global cerebral ischemia. Administration of RoboN, the soluble receptor for Slit, exacerbated the acute chemotactic response to TNFα. These findings are indicative of a tonic repellant effect of endogenous Slit in brain under acute proinflammatory conditions. Three days of continuous systemic administration of Slit following global ischemia significantly attenuated the delayed neuronal death of hippocampal CA1 pyramidal cells. Moreover, Slit abrogated neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation. The ability of Slit to reduce the recruitment of immune cells to ischemic brain and to provide cytoprotective effects suggests that this protein may serve as a novel anti-inflammatory and neuroprotective target for stroke therapy.

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Section: Discussionmentioning

confidence: 99%

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Altay

McLaughlin

et al. 2007

Experimental Neurology

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“…TNF-α expression occurred initially in neurons, and subsequently in glia cells, including microglia and astrocytes as well as in the peripheral immune cells (71)(72)(73). Clinical studies have shown that TNF-α-positive cells localize in all ischemic brains of patients who experienced a severe stroke 3 days post-stroke and remain <15 months post-stroke, and the majority of the increased TNF-α are derived from microglia and macrophages (74,75).…”

Section: Role Of Cytokines In Cerebral Injury Following Ca and Resuscmentioning

confidence: 99%

Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation

et al. 2016

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Abstract. Cardiac arrest (CA) is a leading cause of fatality and long-term disability worldwide. Recent advances in cardiopulmonary resuscitation (CPR) have improved survival rates; however, the survivors are prone to severe neurological injury subsequent to successful CPR following CA. Effective therapeutic options to protect the brain from CA remain limited, due to the complexities of the injury cascades caused by global cerebral ischemia/reperfusion (I/R). Although the precise mechanisms of neurological impairment following CA-initiated I/R injury require further clarification, evidence supports that one of the key cellular pathways of cerebral injury is inflammation. The inflammatory response is orchestrated by activated glial cells in response to I/R injury. Increased release of danger-associated molecular pattern molecules and cellular dysfunction in activated microglia and astrocytes contribute to ischemia-induced cytotoxic and pro-inflammatory cytokines generation, and ultimately to delayed death of neurons. Furthermore, cytokines and adhesion molecules generated within activated microglia, as well as astrocytes, are involved in the innate immune response; modulate influx of peripheral immune and inflammatory cells into the brain, resulting in neurological injury. The present review discusses the molecular aspects of immune and inflammatory mechanisms in global cerebral I/R injury following CA and CPR, and the potential therapeutic strategies that target neuroinflammation and the innate immune system.

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“…This then decreased at 6 and 24 h, only to reincrease at 3 days. 2 Moreover, focal cerebral ischemia in rats results in elevated TNF-a mRNA and protein in ischemic neurons. 3 In human victims of fatal ischemic stroke, cells throughout the brain show TNF-a immunoreactivity during the different phases of focal cerebral infarction with no or incomplete recanalization.…”

Section: Introductionmentioning

confidence: 99%

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model

et al. 2006

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Study design: Randomized study. Objectives: To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-a production. Setting: Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. Methods: Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-a. Results: The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-a in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. Conclusion: Thalidomide treatment before ischemic insult reduces early phase ischemia/ reperfusion injury of the spinal cord in rabbits.

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Induction of Tumor Necrosis Factor-α in the Mouse Hippocampus following Transient Forebrain Ischemia

Cited by 155 publications

References 40 publications

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model

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