Collagenase-induced intracerebral hemorrhage in rats.

Rosenberg, Gary A.; Mun-Bryce, Sheila; Wesley, Mary H.; Kornfeld, Mario

doi:10.1161/01.str.21.5.801

Cited by 537 publications

(398 citation statements)

References 30 publications

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“…Bacterial collagenase model: Injection of bacterial collagenase into the basal ganglia of rats to breakdown the basal lamina of blood vessels was first introduced in the early 1990s (Clark et al, 1998;Rosenberg et al, 1990). In the collagenase model, bleeding begins around 10 minutes after injection, but develops slowly into a full hematoma 4 to 24 hours later (Rosenberg et al, 1990).…”

Section: Autologous Blood Modelmentioning

confidence: 99%

“…In the collagenase model, bleeding begins around 10 minutes after injection, but develops slowly into a full hematoma 4 to 24 hours later (Rosenberg et al, 1990). An advantage of this simple and reproducible model is that the hemorrhage occurs from in situ vessels (Wang and Tsirka, 2005), and it may imitate hematoma expansion (the bleeding-rebleeding phenomenon).…”

Section: Autologous Blood Modelmentioning

confidence: 99%

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Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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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.

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Section: Autologous Blood Modelmentioning

confidence: 99%

Section: Autologous Blood Modelmentioning

confidence: 99%

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Kirkman

Allan

Parry‐Jones

2011

J Cereb Blood Flow Metab

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“…We adapted the collagenase-induced ICH model (Rosenberg et al, 1990) previously described in mice (Choudhri et al, 1997;Clark et al, 1998). Briefly, mice were anesthetized with an intraperitoneal injection of ␣-chloralose (40 mg/kg) and urethane (400 mg/kg) and positioned prone in a stereotaxic head frame (Stoelting, Kiel, WI, U.S.A.).…”

Section: Intracerebral Hemorrhage Inductionmentioning

confidence: 99%

MMP-9 Deficiency Enhances Collagenase-Induced Intracerebral Hemorrhage and Brain Injury in Mutant Mice

Tang

Zhou

et al. 2004

J Cereb Blood Flow Metab

160

141

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Summary:Matrix metalloproteinase-9 (MMP-9) participates in the disregulation of blood-brain barrier during hemorrhagic transformation, and exacerbates brain injury after cerebral ischemia. However, the consequences of long-term inhibition or deficiency of MMP-9 activity (which might affect normal collagen or matrix homeostasis) remains to be determined. The authors investigated how MMP-9 gene deficiency enhances hemorrhage and increases mortality and neurologic deficits in a collagenase-induced intracerebral hemorrhage (ICH) model in MMP-9-knockout mice. MMP-9-knockout and corresponding wild-type mice at 20 to 35 weeks were used to model an aged population (because advanced age is a significant risk factor in human ICH). Collagenase VII-S (0.5 L, 0.075 U) was injected into the right basal ganglia in mice and mortality, neurologic deficits, brain edema, and hemorrhage size measured. In addition, MMP-9 activity, brain collagen content, blood coagulation, cerebral arterial structure, and expressions of several MMPs were examined. Increased hemorrhage and brain edema that correlated with higher mortality and neurologic deficits were found in MMP-9-knockout mice. No apparent structural changes were observed in cerebral arteries, even though brain collagen content was reduced in MMP-9-knockout mice. MMP-9-knockout mice did exhibit an enhanced expression of MMP-2 and MMP-3 in response to ICH. The results indicate that a deficiency of MMP-9 gene in mutant mice increases collagenase-induced hemorrhage and the resulting brain injury. The intriguing relationship between MMP-9 deficiency and collagenase-induced ICH may reflect the reduction in collagen content and an enhanced expression of MMP-2 and MMP-3. Key Words: MMP-9-Intracerebral hemorrhage-Collagenase-Edema-Blood-brain barrier-Coagulation.Spontaneous intracerebral hemorrhage (ICH) is one of the most serious stroke events, and results in high mortality and morbidity in patients (Bernardini and DeShaies, 2001;Panagos et al., 2002;Woo and Broderick, 2002). Mortality in ICH is often as high as 50% within the first month after ICH, with 50% of these deaths occurring within 48 hours (Broderick, 1993). The mechanisms of ICH-induced early brain injury (e.g. brain edema) have been investigated (Altumbabic et al., 1998;Del Bigio et al., 1999;Xi et al., 2002); however, the complete etiology of early brain injury in ICH is incompletely understood.Matrix metalloproteinases (MMPs) are involved in the pathogenesis of cerebral vascular disorders, particularly the formation and rupture of aneurysms. For example, pro-MMP-2 has been implicated as a significant component within arterial walls of intracerebral aneurysms that leads to subarachnoid hemorrhage (Todor et al., 1998). Other studies also support elevated MMP (elastase and collagenase) activity in ruptured vessels in subarachnoid hemorrhage but not in unruptured aneurysms (Gaetani et al., 1999). MMPs are also involved in the hemorrhagic transformation after cerebral ischemia, especially after thrombolysis (Hosomi et al., 2001;M...

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“…Previous studies have reported traumatic brain injury with models such as injections of autologous blood, balloon distension, inertial acceleration, force impact and cold (Finnie and Blumberg, 1990). Rosenberg et al (1990) have established the collagenase-induced intracerebral hematoma model, which is highly reproducible and shows many characteristics of the intracerebral hemorrhagic process in mammals. Only one recent paper has shown that collagenase-induced thalamic lesions can cause central pain in rats (Wasserman and Koeberle, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Since most analgesics have anti-inflammatory properties (Ferland et al, 2007), no analgesics were administered postoperatively since this could change the outcome of the study. We also wanted to reproduce the Rosenberg model in which no analgesic is administered either pre-or post-operatively (Rosenberg et al, 1990).…”

Section: Surgical Methodsmentioning

confidence: 99%

An Induced Hematoma in Caudoputamen Nuclei in Rats Causes Central Pain when the Thalamus is also Implicated and the Central Sensitization is Reversed with Gabapentin

Allam¹

2012

American Journal of Animal and Veterinary Sciences

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Problem statement:The objective of this study was to evaluate pain sensitisation in rats following the induction of an intracerebral hemorrhage by injecting a collagenase solution in the caudoputamen nucleus of the right basal ganglia and to evaluate gabapentin as an analgesic for central pain. Approach: Thirty male Sprague-Dawley rats weighing between 175-300 g were used. In a first experiment, 3 groups of 6 animals were used to evaluate pain threshold using the Hargreaves test (thermal sensitivity) only. Following 3 days of behavioral testing (baseline values), animals in each group were injected intracerebrally either with 0.5, 1 or 2 µL of a collagenase solution (0.5 U 2 µL −1 Type VII collagenase) inducing a hematoma in the right caudoputamen nucleus and/or thalamus. They were then tested for the next 9 consecutive days. In a second experiment, gabapentin was evaluated for the reversal of thermal hyperalgesia and mechanical allodynia (using von Frey filaments) following the intracerebral injection of 3 µL of the collagenase solution. Results: No pain-related behavioral changes were observed following injections with 0.5 and 1 µL of the collagenase solution. However with 2 µL, reaction times were significantly faster on days 3-7 in the right and left hind paws compared to baseline values. The lesion was localized only in the caudoputamen nucleus for animals receiving 0.5 and 1 µL of collagenase whereas lesions extended in the ipsilateral thalamic nuclei (lateral-dorsal and lateral-posterior nuclei) for animals receiving 2 µL of collagenase. Gabapentin reversed mechanical allodynia and thermal hyperalgesia in animals with caudoputamen and thalamic lesions. Conclusion: These preliminary results suggest that central pain was induced in rats with a collagenase-induced intracerebral hemorrhage localized in the thalamus and that mechanical allodynia and thermal hyperalgesia were reduced with gabapentin treatment.

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Collagenase-induced intracerebral hemorrhage in rats.

Cited by 537 publications

References 30 publications

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

MMP-9 Deficiency Enhances Collagenase-Induced Intracerebral Hemorrhage and Brain Injury in Mutant Mice

An Induced Hematoma in Caudoputamen Nuclei in Rats Causes Central Pain when the Thalamus is also Implicated and the Central Sensitization is Reversed with Gabapentin

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