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Baker Institute |  Faculty



Chris B. Schaffer, PhD
Assistant Professor of Biomedical Engineering

Schaffer Group, Dept. of Biomedical Engineering, Cornell University

Clinical evidence shows that ischemic and hemorrhagic microvascular lesions in the brain play an important role in elderly dementia, but few effective treatment or preventative strategies exist. This deficit is due, in part, to a lack of good animal models of these small-scale strokes that would allow the progression of disease to be studied and would provide a platform for the evaluation of therapeutics. The Schaffer group uses advanced optical techniques to induce targeted, single-vessel occlusions and hemorrhages in the cortex of live, anesthetized rats, as a means to provide a comprehensive animal model of small-scale stroke.

The group’s research uses in vivo two-photon fluorescence microscopy to image the brain vasculature and quantify blood flow. Two different optical technologies are used to produce microvessel lesions. In the first, tightly-focused optical excitation of a blood-borne photosensitizer triggers localized clot formation in a specifically targeted vessel on the surface of the brain. In the second, highly nonlinear absorption of femtosecond-duration laser pulses in a targeted vessel beneath the surface of the brain causes either clot formation, vascular rupture (see Figure), or transient leakage of blood, depending on the incident laser parameters.

The goal of our research is to determine the effect of these microvascular lesions on the health and functionality of brain tissue. We measure the change in blood flow in upstream and downstream vessels that results from single-vessel occlusions at different locations in the vasculature, from arterioles, to capillaries, to venules, and identify the most vulnerable locations. We characterize the long-term effects on blood flow and vascular permeability of a microvascular clot or microhemorrhage through repeated imaging of a lesioned animal over several weeks. We characterize the pathological changes caused by these microvascular lesions using post-mortem immunohistology and electron microscopy and correlate the severity of the pathology with the degree of blood flow decrease and/or extent of hemorrhage. Finally, we develop new optical techniques that allows in vivo studies of physiological changes in neurons and other brain cells following a localized microvascular lesion.

These data will provide an understanding of the effect of microvascular clots and hemorrhages on the viability of neural cells and will open the door to therapeutic possibilities to treat diseases such as lacunar stroke.

 

Microhemorrhages in human and rat. a) and b) A microhemorrhage in human hippocampus thought be about 6 days old. Bright granular blue is haem-rich deposit stained with Prussian blue, while vessels are stained with cressyl violet in (a). Autofluorescence indicates fresh haem deposit and scattered erythrocytes in (b). c) Hemorrhage of microvessel in rat cortex induced by ultrashort-pulse laser irradiation. Endogenous peroxidase in erythrocytes is stained brown by diaminobenzadine (DAB) and neurons are stained with Nissl. Animal was sacrificed about 2 hours after hemorrhage induction. Data in parts (a) and (b) adapted from K. M. Cullen, et al., J. Cereb. Blood Flow Metab 25, 1656 (2005).

Microhemorrhages in human and rat. a) and b) A microhemorrhage in human hippocampus thought be about 6 days old. Bright granular blue is haem-rich deposit stained with Prussian blue, while vessels are stained with cressyl violet in (a). Autofluorescence indicates fresh haem deposit and scattered erythrocytes in (b). c) Hemorrhage of microvessel in rat cortex induced by ultrashort-pulse laser irradiation. Endogenous peroxidase in erythrocytes is stained brown by diaminobenzadine (DAB) and neurons are stained with Nissl. Animal was sacrificed about 2 hours after hemorrhage induction. Data in parts (a) and (b) adapted from K. M. Cullen, et al., J. Cereb. Blood Flow Metab 25, 1656 (2005).

 

 

Typing.


 Chris B. Schaffer

Contact Information:
Office: 607-256-5620
Fax: 607-256-5608
E-mail: cs385@cornell.edu