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Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury
Author(s) -
Quintana Albert,
Giralt Mercedes,
Rojas Santiago,
Penkowa Milena,
Campbell Iain L.,
Hidalgo Juan,
Molinero Amalia
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20680
Subject(s) - tumor necrosis factor alpha , proinflammatory cytokine , gliosis , tumor necrosis factor receptor 1 , medicine , cytokine , inflammation , immunology , biology , pathology , tumor necrosis factor receptor
Tumor necrosis factor‐α (TNF‐α) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF‐α can induce both apoptosis and necrosis via intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type‐1 receptor (TNFR1) and type‐2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild‐type (WT) animals and in mice lacking TNFR1 (TNFR1 KO) or TNFR2 (TNFR2 KO). Lack of TNFR1, but not of TNFR2, significantly decreased the inflammatory response and tissue damage elicited by the cryolesion at both 3 and 7 days postlesion, with decreased gliosis, lower IL‐1β immunostaining, and a reduction of apoptosis markers. Cryolesion produced a clear induction of the proinflammatory cytokines interleukin (IL)‐1α, IL‐1β, IL‐6, and TNF‐α; this induction was significantly lower in the TNFR1 KO mice. Host response genes (ICAM‐1, A20, EB22/5, and GFAP) were also induced by the cryolesion, but to a lesser extent in TNFR1 KO mice. Lack of TNFR1 signaling also affected the expression of apoptosis/cell death‐related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected by TNFR1 deficiency. Overall, these results suggest that TNFR1 is involved in the early establishment of the inflammatory response and that its deficiency causes a decreased inflammatory response and tissue damage following brain injury. © 2005 Wiley‐Liss, Inc.