Lobar Intracerebral Hemorrhage Model in Pigs

574

609

Intracerebral hemorrhage (ICH) is a devastating clinical event without effective therapies. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury. Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species. Better understanding of the role of the ICH-induced inflammatory response and its potential for modulation might have profound implications for patient treatment. In this review, a summary of the available literature on the inflammatory responses after ICH is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies. In the near future, additional strategies that target inflammation could offer exciting new promise in the therapeutic approach to ICH.

Section: Animal Models Of Intracerebral Hemorrhagementioning

confidence: 99%

Inflammation after Intracerebral Hemorrhage

Wang

Doré

2007

574

609

“…Initially used in rats in the 1980s Nath et al, 1986), this model was later adapted for use in rabbits (Kaufman et al, 1985), dogs (Qureshi et al, 2001a), pigs (Wagner et al, 1996), and mice (Nakamura et al, 2004b). Blood is taken from a superficial vessel and stereotactically injected into the brain, usually into the striatum as injections into the cortex are often complicated by SAH (subarachnoid hemorrhage) and thus inconsistent hematoma volumes .…”

Section: Autologous Blood Modelmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension-and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.

“…Heme (or ferroprotoporphyrin IX) is generated as a breakdown product of hemoglobin and other hemoproteins arising from traumatic subarachnoid hemorrhages, intraparenchymal contusions, and hematomas ( Figure 1) Macdonald and Weir, 1991;Wagner et al, 2003Wagner et al, , 1996Xi et al, 1998). Given the pathogenicity of heme (Huang et al, 2002;Maines and Trakshel, 1993;Regan and Panter, 1996;Ryter and Tyrrell, 2000;Wu et al, 2002), it is surprising that few studies have examined its role in the setting of TBI.…”

Section: Introductionmentioning

confidence: 99%

Heme Regulation in Traumatic Brain Injury: Relevance to the Adult and Developing Brain

Chang

Claus

Vreman

et al. 2005

Intracranial bleeding is one of the most prominent aspects in the clinical diagnosis and prognosis of traumatic brain injury (TBI). Substantial amounts of blood products, such as heme, are released because of traumatic subarachnoid hemorrhages, intraparenchymal contusions, and hematomas. Despite this, surprisingly few studies have directly addressed the role of blood products, in particular heme, in the setting of TBI. Heme is degraded by heme oxygenase (HO) into three highly bioactive products: iron, bilirubin, and carbon monoxide. The HO isozymes, in particular HO-1 and HO-2, exhibit significantly different expression patterns and appear to have specific roles after injury. Developmentally, differences between the adult and immature brain have implications for endogenous protection from oxidative stress. The aim of this paper is to review recent advances in the understanding of heme regulation and metabolism after brain injury and its specific relevance to the developing brain. These findings suggest novel clinical therapeutic options for further translational study.