Effect of Interleukin-1 on Traumatic Brain Injury–Induced Damage to Hippocampal Neurons

Abstract

Interleukin-1 (IL-1) has many roles in the brain in addition to mediating inflammatory processes in the glia, and has also been implicated in neurodegenerative disease. Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality in young persons. We conducted a study to assess the effect of IL-1 on the TBI-induced death of hippocampal neurons. After TBI was induced in adult male Sprague-Dawley rats under anesthesia, we evaluated neuronal damage score through microscopic examination and Pulsinelli's grading system. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to measure the levels of IL-1alpha and IL- 1beta in brain tissue at different points after the induction of TBI. Over a 4-day period, the specific sites of release of IL-1alpha and IL-1beta in the brain were elucidated by immunocytochemistry with double- labeling. TBI to the hippocampus was followed by disruption of the blood-brain barrier and severe neuronal loss. Levels of IL-1alpha RNA and protein were significantly elevated at 3 h after TBI, peaked at 12 h, and remained elevated for 168 h. IL-1beta RNA and protein expression were also elevated at 3 h after TBI, but remained so only for 48 h. Our findings indicate that the observed TBI-induced increases in IL-1alpha and IL-1beta occur largely through release of these cytokines from neurons and astrocytes, respectively. Intraventricular administration of antibodies to IL-1alpha and IL-1beta before TBI significantly attenuated the TBI-induced loss of hippocampal neurons. These results show that IL-1alpha and IL-1beta play important roles in the TBI-induced loss of hippocampal neurons.

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

“…The increase in IL-1 after traumatic brain injury is followed by neuronal loss. IL-1 is linked to the loss because antibodies to IL-1 attenuate neuronal loss [36] and in IL-1 deficient mice neuronal loss and infarct volumes are reduced [6]. The early primary source of IL-1 is microglia, but later the cytokine is also produced by astrocytes and expression in oligodendrocytes and neurons has also been detected [59].…”

Blockade of Peroxynitrite-Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug-Releasing Polymer

“…pathology: the swift development of toxicity and inflammation at the injury epicenter that can jeopardize the initial survival and repair potential of the donor cells [38]. Post-injury pathophysiology usually involves two processes: the primary injury, mostly caused by mechanical insults, and the secondary injury events (within minutes to weeks or even months after SCI), in which heightened release of pro-inflammatory cytokines (e.g., TNF-α and IL-1β) [39][40][41]; oxidative stress, ischemia, and free radicals produced by leukocytes, macrophages and microglia; glutamate metabolism impairment due to cytokines and free radicals leading to excitatory cytotoxicity [42,43]; breakdown of the blood-brain barrier and neural tissues by phospholipase A2, arachidonic acid, eicosanoids, extracellular matrix-degrading enzymes such as metalloproteinase [1,[44][45][46][47][48]; pathological autoimmune response mediated by activated lymphocytes; all leading to protein nitration, breaking down of lipids and nucleic acids, demyelination and apoptosis as well as neuroinflammation. This complex cascade of interactive events not only exacerbates tissue/cell loss, but also impedes repair mechanisms through, for instance, limiting the survival of the donor cells [49].…”

Cerebral microdialysis of interleukin (IL)-1ß and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats

“…This pluripotent, pro-inflammatory cytokine participates in a complex network of signalling molecules and seems to be one of the most important factors in the propagation and maintenance of the inflammatory cascade after TBI, being responsible for enhancing the activation of T-cells [3,8,20,27]. IL-1 ß belongs to the IL-1 family which has three wellknown endogenous ligands, two agonists, IL-1α and IL-1 ß, and one IL-1 receptor antagonist [23].…”