Inflammation after Intracerebral Hemorrhage

649

533

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

Section: Intracerebral Hemorrhagementioning

confidence: 99%

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

Lauritzen

Dreier

Fabricius

et al. 2010

649

533

“…3 Therefore, to improve the clinical outcome of ICH and better understand its pathogenesis, induced brain injury is in high demand. 1 Several lines of evidence suggest that glutamate is involved in the secondary damage of ICH. Thus, transient elevation of the extracellular concentration of glutamate in the perihematomal region was shown in animal models of ICH induced by means of injection of autologous blood or collagenase into the basal ganglia.…”

Section: Introductionmentioning

confidence: 99%

“…1 It is a type of acute stroke characterized by extravasation of blood into the brain parenchyma and formation of hematoma. Hematoma produces primary damage because of the toxic effect of thrombin, a mass effect due to the extravasated blood that compresses the surrounding brain tissue; sometimes, this damage is also enhanced by rebleeding.…”

Section: Introductionmentioning

confidence: 99%

Blood Glutamate Grabbing Does Not Reduce the Hematoma in an Intracerebral Hemorrhage Model but it is a Safe Excitotoxic Treatment Modality

Silva‐Candal

Vieites‐Prado

Gutiérrez-Fernández

et al. 2015

Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging. Keywords: blood glutamate grabbing; GOT; intracerebral hemorrhage; oxaloacetate; protection INTRODUCTION Intracerebral hemorrhage (ICH) represents approximately 15% of all strokes; moreover, the incidence of ICH is expected to grow, given the increase in the use of anticoagulants and aging of the population. Journal of Cerebral Blood1 It is a type of acute stroke characterized by extravasation of blood into the brain parenchyma and formation of hematoma. Hematoma produces primary damage because of the toxic effect of thrombin, a mass effect due to the extravasated blood that compresses the surrounding brain tissue; sometimes, this damage is also enhanced by rebleeding. Primary damage is followed by a secondary damage mainly characterized by edema formation, tissular ischemia, and glutamate excitotoxicity.

“…15 Inflammation has an important role in ICH-induced brain injury. 16 This study investigates the effect LCN2 deficiency on the expression of ferritin (an iron storage protein), microglia activation, neuronal death, and neurologic deficits in a mouse model of ICH. In addition, the role of LCN2 in iron-induced brain injury was also examined.…”

Section: Introductionmentioning

confidence: 99%

Role of Lipocalin-2 in Brain Injury after Intracerebral Hemorrhage

Zheng

et al. 2015

Lipocalin-2 (LCN2) is a siderophore-binding protein involved in cellular iron transport and neuroinflammation. Both iron and inflammation are involved in brain injury after intracerebral hemorrhage (ICH) and this study examined the role of LCN2 in such injury. Male adult C57BL/6 wild-type (WT) or LCN2-deficient (LCN2 − / − ) mice had an intracerebral injection of autologous blood or FeCl 2 . Control animals had a sham operation or saline injection. T2-weighted magnetic resonance imaging and behavioral tests were performed at days 1, 3, 7, 14, and 28 after injection. In WT mice, brain LCN2 levels were increased in the ipsilateral basal ganglia after ICH or iron injection. Lipocalin-2-positive cells were astrocytes, microglia, neurons, and endothelial cells. Intracerebral hemorrhage resulted in a significant increase in ferritin expression in the ipsilateral basal ganglia. Compared with WT mice, ICH caused less ferritin upregulation, microglia activation, brain swelling, brain atrophy, and neurologic deficits in LCN2− / − mice (P o0.05). The size of the lesion induced by FeCl 2 injection as well as the degree of brain swelling and blood-brain barrier disruption were also less in LCN2− / − mice (P o 0.05). These results suggest a role of LCN2 in enhancing brain injury and iron toxicity after ICH.