Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry

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✓ Experimental intracerebral hemorrhage has been shown to cause extensive cerebral ischemia. This study was performed to ascertain the time course of these changes and also to examine the type of brain damage that may occur under such circumstances. Halothane anesthesia was induced in rats, and 25 µl autologous blood was injected into the caudate nucleus; the effects were studied with autoradiographic measurement of local cerebral blood flow and capillary permeability, and also by light microscopy and histochemical techniques. Blood flow returned to normal or to slightly increased levels within the first 3 hours, and ischemic levels of flow were found to persist only to a marginal degree beyond 10 minutes after the lesions were made. Capillary permeability was maximum during the first 30 minutes after the hemorrhage and diminished with time. Structural evidence of ischemic damage was localized to the cortex overlying the hemorrhage, but was not seen in the caudate nucleus. Nevertheless, histochemical investigation did reveal an area of disturbed enzyme function in the striatum. This finding of biochemical disturbance without structural evidence of ischemic damage reveals that there is an area around the hematoma that, although demonstrating disturbed function, does not show structural damage, and the milieu of this partially injured brain may be implicated in the delayed development of the ischemic brain damage that follows intracerebral hemorrhage in man.

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Address reprint requests to: A. David Mendelow, Ph.D., F.R.C.S., Department of Neurosurgery, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne NE4 6BE, England.

© AANS, except where prohibited by US copyright law.

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    After injection of 25 µl blood into the right caudate nucleus, rat brains were perfusion-fixed with a formaldehyde/acetic acid/methanol solution and sectioned. In these sections of a lesioned brain, a hematoma is visible in the right caudate nucleus (center section) with extravasation laterally into the white matter of the corpus callosum. The hematoma appears black. There is evidence of Evans blue dye extravasation into the caudate nucleus around the hematoma, visible as a gray discoloration on the upper and center sections.

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    Tracings of cerebral perfusion pressure (CPP) during the first 3 hours after hemorrhage. No significant change in perfusion pressure was seen in the lesioned group compared to the control (sham-operated) group.

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    Distribution of cerebral blood flow (CBF) at different times in five lesioned and five control (sham-operated) animals. The y axis expresses the cumulative percentage of the hemisphere at particular flow values expressed on the x axis in steps of 25 ml/100 gm/min. a: At 1 minute, the CBF curve of the lesioned group has shifted to the left of the control curve, indicating that a greater percentage of the hemisphere in this section has a reduced blood flow. b: At 10 minutes, blood flow is returning toward normal and the curve of the lesioned group is now biphasic in relation to that of the control group. c: At 3 hours, the CBF curve of the lesioned group has shifted to the right of that of the control group, indicating that there is an overall increase in flow. d: Comparison of three CBF curves in the lesioned group showing that the 3-hour curve has shifted to the right of the 1-minute and 10-minute curves.

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    Carbon-14-labeled iodoantipyrine autoradiographs in the three time groups. Left Column: Sections from the lesioned group. The 25-µl lesions are seen as white areas in the right caudate nucleus. At 1 minute, cortical ischemia (white area) is also visible. At 10 minutes, the cortical flow is returning to normal but an area of persisting caudate hypoperfusion is seen in the right caudate nucleus, and cortical flow is no longer at an ischemic level. Right Column: Time-matched sham-operated control group. At 1 minute, a minor area of hypoperfusion is seen in the right caudate nucleus at the site of needle insertion. At 10 minutes and 3 hours, the needle track is seen as a faint gray area of hypoperfusion in the mid caudate region.

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    Carbon-14-labeled aminoisobutyric acid (14C-AIB) autoradiographs. The right caudate nucleus is the lesion site. Upper Left: Section obtained 25 minutes after lesioning. There is extensive extravasation of 14C-AIB in the right caudate region. Upper Right: In this 25-minute control section a small intense lesion is seen in the caudate at the site of needle insertion. Lower Left: Section obtained 3 hours after lesioning. The right caudate shows minimal 14C-AIB uptake compared to the earlier lesioned brain. Lower Right: In this 3-hour control section, there is an area of localized increased 14C-AIB uptake in the right caudate nucleus but clearly less than in the control section obtained at 25 minutes.

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    Comparison of the product of size and intensity of the lesions as visualized on 14C-aminoisobutyric acid autoradiography. The 25-minute lesion group has a greater value than the control group. This was not apparent at 3 hours, when the lesion group clearly had smaller and less intense lesions than the time-matched control group. There is a clear trend toward smaller less intense lesions with the passage of time.

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    Neuropathological charting of the distribution of ischemic damage (black area) in a lesioned animal (left) and a sham-operated control animal (right). Comparing the right hemispheres (lesioned side) in each animal, the damage is principally at the cortical level, and is minimal in the control animal but obvious in the lesioned animal. The left hemisphere in each animal shows a linear area of ischemic damage at the site of the ventricular catheter.

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    Sections stained with glycogen phosphorylase (left column) compared to adjacent sections prepared for 14C-iodoantipyrine autoradiography (right column). There is an area of obvious depression of phosphorylase activity in the right caudate (lesioned side) at each time of study. The area of hypoperfusion seen in each autoradiogram corresponds to the site of phosphorylase depletion.

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