Laboratory For Cerebrovascular Biophysics
Cerebral Vasospasm Studies

Dr Peterson | Recent Publications | Links

Research in Cerbral Vasospasm Dr Peterson's Labs - Studies in Protein Kinase C (PKC). Dr J.W. Peterson Laboratory For Cerebrovascular Biophysics Dr Zervas's Lab - PET Imaging of CBF, CBV, O2M, OEF and GluMetab Research @ Neurosurgery Dr N.T. Zervas, Research Info Neurosurgery Surgical Research Lab Neurosurgery Research Labs Images courtesy of Anna-Liisa Brownell, PhD in collaboration on a study of CNS tissue metabolism (rGMR, rCMRO2, rOEF, rCBF, rCBV) during cerebral vasospasm. (For more info.) Research PET Imaging Functional CT Studies Images courtesy of CIPR (Center for Imaging and Pharmaceutical Research) as part of a collaboration with the CNS project group. The images are the work of George Hunter, MD and Leena Hamberg, PhD as part of a study on peripheral tissue perfusion (CBV, TTT, CBFi) during cerebral vasospasm. (For more info.) Center for Imaging and Pharmaceutical Research (CIPR) Dr Zervas's & Dr Peterson's Labs - Studies in laser-induced pulsed-fluid wave treatment of vasospastic cerebral arteries. MGH Laser Center

Cerebral vasospasm after subarachnoid hemorrhage leads to mortality and disability in a large number of patients annually. The basic mechanisms by which adventitial blood clot produces chronic cerebral arterial constriction are not well understood; consequently, therapy has been only partially effective. The main research goal then has been to isolate and define those processes most important to the development of this pathology, so that truly effective pharmacological intervention can be devised.

Previous studies in the laboratory have shown that the erythrocyte component of subarachnoid blood is essential to the process. Lysis of those erythrocytes and release of vasoactive hemoglobin is a potent contributor. In vitro studies of human and animal erythrocytes have shown that these cells, which incubated under conditions which mimic subarachnoid blood clot, become immunologically reactive: activating the complement protein cascade leading ultimately to formation of "membrane attack complex" and erythrocyte lysis. Other effects of complement activation include stimulation of inflammation (which additionally contributes significantly to vasoconstriction) and increased vascular permeability (which acts to reinforce the cycle by admitting increased amounts of complement protein).

The laboratory is currently purifying various complement factors in our animal model and using radiolabelled materials to monitor movement into and accumulation in the subarachnoid clot (in particular C5, C8 and C9). The laboratory plans then to produce specific antibodies against these factors to observe the effect of specific decomplementation on the development of cerebrovascular constriction and perivascular inflammation.

Other studies in our laboratory focus on the specific mechanisms which activate smooth muscle contraction in cerebral arteries. Early studies suggest that agonists which activate long-lasting constriction may work though the diacylglycerol (DAG)-activated protein kinase C (PKC) system. Using in vitro methods we are studying DAG levels and PKC activity in cerebral vessels and the connection between these factors and the long lasting vasoconstriction which is the hallmark pathology of cerebral vasospasm. In particular, we hope to clarify the extent to which the vasoactivity of hemoglobin is expressed through this system.

 

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