Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.

Holland, J P; Sydserff, S G; Taylor, W A; Bell, B. Anthony

doi:10.1161/01.str.25.10.2055

Cited by 26 publications

(10 citation statements)

References 24 publications

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“…AM tended to suppress the reduction in regional cerebral blood flow after middle cerebral artery occlusion, and inhibited the increase in myeloperoxidase activity (i.e., decreased the number of infiltrating neutrophils) in the ischemic area, which led to significantly decreased brain injury (80,88). These results are very similar to the data reported for CGRP administration (89). On the other hand, intracerebroventricular administration of a high dose of AM before and after occlusion of the middle cerebral artery has been shown to cause a significant increase in the degree of focal cerebral injury (75).…”

Section: Am and Cerebral Ischemiasupporting

confidence: 86%

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

et al. 2003

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Section: Am and Cerebral Ischemiasupporting

confidence: 86%

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

et al. 2003

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“…i.v. administration of CGRP, a related vasodilator, can produce a significant improvement in ischemic blood flow to cerebral ischemic tissue and reduce brain injury after focal stroke (35). However, dilation of the microcirculation at the site of injury may also facilitate inflammatory cell infiltration that occurs in the ischemic cortex shortly after MCAO (20,36,37).…”

Section: Resultsmentioning

confidence: 99%

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Wang

Yue

Barone

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

185

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Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (12II-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dosedependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.Adrenomedullin (AM) is a recently discovered peptide that was initially identified from human pheochromocytoma (1). Biologically active AM consists of 52 amino acids in humans and 50 amino acids in rats (1, 2), and both AMs exhibit potent vasodilator activity in vitro and in vivo (3-6). AM bears homology to a family of peptides that includes calcitonin gene-related peptide (CGRP) (7-10) and amylin (11,12). CGRP is a widely distributed neuropeptide best known for its potent vasodilator actions (13-15) and its effect on insulin functions (16). Amylin is the major protein found in islet amyloid (11, 16) in humans with non-insulin-dependent diabetes mellitus. CGRP and amylin have been found to have a wide range of biological activities, including energy metabolism, central nervous system and cardiovascular functions, and calcium metabolism (for review see refs. 16 and 17). In contrast, little is known of the biological function of AM beyond vasodilation. In contrast to CGRP, AM mRNA and peptide have not been detected in normal brain (1, 2). Very recently, AM has been associated with congestive heart failure, since elevated levels of AM were found in cardiac tissue of the failing hearts (18).In the present report, we used a recently developed mRNA differential display technique (19) to identify genes expressedThe publication costs of this article were defrayed in part by page charge payment. Th...

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“…The brain is protected as a priority following TBI as the result of stress response. CGRP is one of the most essential molecules in this stress protection (22). The peripheral CGRP concentrates in the brain tissue due to the disruption of the blood-brain barrier following TBI.…”

Section: Discussionmentioning

confidence: 99%

Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury

Song

Zhang

et al. 2011

Mol Med Report

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Abstract. The mechanisms responsible for the phenomenon of an accelerated speed of fracture healing in patients with traumatic brain injury (TBI) remain unclear. The present study was performed to test the hypothesis that TBI causes changes in calcitonin gene-related peptide (CGRP) levels in sera that enhance fracture healing. A standard closed femoral fracture was produced in rats, which were subjected to additional closed head trauma. The fracture healing was assessed 4 and 8 weeks later using micro-CT. Sera, brain tissues and muscles surrounding the fracture sites collected at 24, 48, 72 and 168 h after injury were used to detect the expression of CGRP using ELISA, immunohistochemistry and RT-PCR. Micro-CT demonstrated that fracture healing and mineralization in the TBI-fracture group occurred earlier compared to the fracture-only group. ELISA analysis revealed a high concentration of CGRP in the TBI-fracture group (P<0.05), and immunohistochemistry assay and RT-PCR analysis revealed a significant increase in CGRP in the brain and muscle of the TBI-fracture group at 168 h after fracture (P<0.001). Our results indicate that the mechanism for the enhancement of fracture-healing secondary to traumatic brain injury is correlated to the high levels of CGRP, which may be released from the brain tissue into the serum.

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Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.

Cited by 26 publications

References 24 publications

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury

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