TNFα gene expression is induced in neurones after a hippocampal lesion

Tchélingérian, Jean‐Léon; Vignais, L.; Jacque, C.

doi:10.1097/00001756-199401000-00013

Cited by 63 publications

(37 citation statements)

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“…The source of this TNF-a in injured spinal cord was not clear, however. It is likely that microglia, reactive astrocytes, neurons, endothelial cells, and infiltrating macrophages may all produce such inflammatory cytokines as TNF-a after injury (Benveniste, 1992;Eng et al, 1992;Knoblach et al, 1999;Lieberman et al, 1989;Morioka et al, 1991;Tchelingerian et al, 1994;Yan et al, 2001). Our results also demonstrated TNF-a immunoreactivity in neurons and presumptive glial cells after SCI.…”

Section: Figsupporting

confidence: 63%

Increased Production of Tumor Necrosis Factor-αInduces Apoptosis after Traumatic Spinal Cord Injury in Rats

Yune¹,

Chang

Kim

et al. 2003

Journal of Neurotrauma

122

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We showed previously that, after spinal cord injury (SCI), tumor necrosis factor-alpha (TNF-alpha) may serve as an external signal, initiating apoptosis in neurons and oligodendrocytes. To further characterize the apoptotic cascade initiated by TNF-alpha after SCI, we examined the expression of TNF-alpha, inducible nitric oxide (NO) synthase (iNOS), and the level of NO after SCI. Western blots and reverse transcription polymerase chain reactions showed an early upregulation of TNF-alpha after injury. A peak TNF-alpha expression was observed within 1 h of injury. By 4 h after injury, the expression of iNOS and the level of NO were markedly increased in the injured spinal cord. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells were also first observed in the lesioned area 4 h after SCI. The largest number of TUNEL-positive cells was observed between 24-48 h after SCI. Injecting a neutralizing antibody against TNF-alpha into the lesion site after injury significantly reduced the expression of iNOS, the level of NO and the number of TUNEL-positive cells in the injured spinal cord. Injecting the NOS inhibitors, N(G)-monomethyl-L-arginine monoacetate and S-methylisothiourea sulfate, or an NO scavenger, carboxy-PTIO, into the lesion site also significantly reduced the level of NO and the degree of DNA laddering in the injured spinal cord. These data suggest that after SCI, apoptosis induced by TNF-alpha may be mediated in part by NO via upregulation of iNOS, induced in response to TNF-alpha.

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Section: Figsupporting

confidence: 63%

Increased Production of Tumor Necrosis Factor-αInduces Apoptosis after Traumatic Spinal Cord Injury in Rats

Yune¹,

Chang

Kim

et al. 2003

Journal of Neurotrauma

122

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“…At the peak of expression, 9-12 days after the lesion, the expression extends to the rest of the cortex (Figure 1d and e), basal ganglia (Figure 1g and h), cerebellum, hippocampus, amygdala, diagonal band of Broca, substantia nigra, hypothalamus and raphe. 37 These data suggest that the IL-1 signal consists of changes in concentration of specific IL-1 family members. The changes are transient and timed to provide IL-1 action in a specific spatio-temporal pattern.…”

Section: Centrally Elicited Cytokine Signalingmentioning

confidence: 91%

Cytokine signals propagate through the brain

et al. 2000

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Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF␣) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNF␣ expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNF␣ expression, elicited centrally or systemically, propagates through brain parenchyma following specific spatio-temporal patterns. We propose that cytokine signals propagate along neuronal projections and extracellular diffusion pathways by molecular cascades that need to be further elucidated. This elucidation is a prerequisite for better understanding of reciprocal interactions between nervous, endocrine and immune systems. Molecular Psychiatry (2000) 5, 604-615.

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“…Up-regulation of TNF-␣ protein and mRNA has been reported to occur in models of cerebral ischemia (38) and in the injured cortex and hippocampus between 1 and 6 h after experimental brain injury (7,8,10). Posttraumatic expression is typically observed before the accumulation of infiltrating immune cells, suggesting that TNF-␣ is synthesized directly by neurons (39)(40)(41). Increased levels of TNF-␣ have also been observed in plasma and cerebrospinal fluid of human headinjured patients (6).…”

Section: Discussionmentioning

confidence: 99%

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Scherbel

Raghupathi

Nakamura

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

377

231

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The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(؊/؊)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(؊/؊) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(؊/؊) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 20; wt, n ‫؍‬ 20] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 15; wt, n ‫؍‬ 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), braininjured TNF(؊/؊) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (P < 0.02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(؊/؊) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(؊/؊) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.

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TNFα gene expression is induced in neurones after a hippocampal lesion

Cited by 63 publications

References 0 publications

Increased Production of Tumor Necrosis Factor-αInduces Apoptosis after Traumatic Spinal Cord Injury in Rats

Increased Production of Tumor Necrosis Factor-αInduces Apoptosis after Traumatic Spinal Cord Injury in Rats

Cytokine signals propagate through the brain

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

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