Interleukin‐1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat

Abstract

The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 g/kg IL-1 (n ‫؍‬ 9) or vehicle (n ‫؍‬ 10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7°C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion.

Morroniside Improves Microvascular Functional Integrity of the Neurovascular Unit after Cerebral Ischemia

“…It is also thought that focal ischemia of the brain is a pro-inflammatory stimulus and that interactions of inflammatory cytokines with components of the neurovasculature are in response to BBB permeability [23]. Our studies supported this hypothesis and identified IL-1β as a stimulus of endothelial permeability, which has been previously postulated to facilitate edema formation during the initial moments following the onset of focal ischemia [35], [36]. On the basis of these results, we conjectured that morroniside regulated cerebrovascular permeability after stroke via the downregulation of MMPs and IL-1β, hence inhibiting edema formation during the initial phase.…”

Systemic Inflammation Alters the Kinetics of Cerebrovascular Tight Junction Disruption after Experimental Stroke in Mice

“…Acute peripheral inflammatory challenge worsens outcome after focal cerebral ischemia (McColl et al, 2007a) and increases hippocampal neuronal death after global cerebral ischemia (Spencer et al, 2007). These effects are independent of core body and brain temperature (Parry-Jones et al, 2008). Systemic inflammation also sensitizes the brain to neonatal hypoxic and hemorrhagic injury (Lehnardt et al, 2003;Xue and Del Bigio, 2005) and exacerbates excitotoxic (Favrais et al, 2007) and traumatic brain injury (Utagawa et al, 2008).…”

Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

“…In the infarct core, reduced blood flow induces the reduction of heat radiation and increased anaerobic metabolism induces the increase in heat production, which may both result in the elevated brain temperature. In IP tissue, reduced blood flow may induce the reduction of heat radiation, while an increase in heat production is induced by the subsequent events, including both aerobic and anaerobic metabolism [19–22], inflammation and the release of excitatory amino acids [23, 24]. These complex processes may account for the higher elevated brain temperature in the IP than in the infarct core or oligemic regions at the artery occlusion stage.…”