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Titolo:
Experimental closed head injury: Analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines
Autore:
Stahel, PF; Shohami, E; Younis, FM; Kariya, K; Otto, VI; Lenzlinger, PM; Grosjean, MB; Eugster, HP; Trentz, O; Kossmann, T; Morganti-Kossmann, MC;
Indirizzi:
Univ Zurich Hosp, Dept Surg, Div Trauma Surg, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Surg, Div Res, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Univ Zurich Hosp, Dept Med, Clin Immunol Sect, CH-8091 Zurich, SwitzerlandUniv Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pharmacol, IL-91010 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91010 -91010 Jerusalem, Israel
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 2, volume: 20, anno: 2000,
pagine: 369 - 380
SICI:
0271-678X(200002)20:2<369:ECHIAO>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FACTOR-ALPHA; TNF-ALPHA; RAT-BRAIN; CEREBROSPINAL-FLUID; RECEPTOR FAMILIES; LYMPHOTOXIN-ALPHA; CEREBRAL-ISCHEMIA; CNS INFLAMMATION;
Keywords:
traumatic brain injury; cytokines; blood-brain barrier; knockout mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
75
Recensione:
Indirizzi per estratti:
Indirizzo: Stahel, PF Univ Zurich Hosp, Dept Surg, Div Trauma Surg, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 rich, Switzerland
Citazione:
P.F. Stahel et al., "Experimental closed head injury: Analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines", J CEREBR B, 20(2), 2000, pp. 369-380

Abstract

Cytokines are important mediators of intracranial inflammation following traumatic brain injury (TBI). In the present study, the neurological impairment and mortality blood-brain barrier (BBB) function, intracranial polymorphonuclear leukocyte (PMN) accumulation, and posttraumatic neuronal cell death were monitored in mice lacking the genes for tumor necrosis factor (TNF)/lymphotoxin-alpha (LT-alpha) (TNF/LT-alpha-/-) and interleukin-6 (IL-6) and in wild-type (WT) littermates subjected to experimental closed head injury (total n = 107). The posttraumatic mortality was significantly increased in TNF/LT-alpha-/- mice (40%; P < 0.02) compared with WT animals (10%). TheIL-6-/- mice also showed a higher mortality (17%) than their WT littermates (5.6%), but the difference was not statistically significant (P > 0.05). The neurological severity score was similar among all groups from 1 to 72 hours after trauma, whereas at 7 days, the TNF/LT-alpha-/- mice showed a tendency toward better neurological recovery than their WT littermates. Interestingly, neither the degree of BBB dysfunction nor the number of infiltrating PMNs in the injured hemisphere was different between WT and cytokine-deficient mice, Furthermore, the analysis of brain sections by in situ DNA nick end labeling (TUNEL histochemistry) at 24 hours and 7 days after head injury revealed a similar extent of posttraumatic intracranial cell death in all animals. These results show that the pathophysiological sequelae of TBI are not significantly altered in mice lacking the genes for the proinflammatory cytokines TNF, LT-alpha, and IL-6, Nevertheless, the increased posttraumatic mortality in TNF/LT-alpha-deficient mice suggests a protective effect of these cytokines by mechanisms that have not been elucidated yet.

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Documento generato il 09/07/20 alle ore 20:40:28