Brain cells manufacture and secrete angiogenic peptides after focal cerebral ischemia, but the purpose of this angiogenic response is unknown. Because the maximum possible regional cerebral blood flow is determined by the quantity of microvessels in each unit volume, it is possible that angiogenic peptides are secreted to generate new collateral channels; other possibilities include neuroprotection, recovery/regeneration, and removal of necrotic debris. If the brain attempts to create new collaterals, microvessel density should increase significantly after ischemia. Conversely, if angiogenic-signaling molecules serve some other purpose, microvessel densities may increase slightly or not at all. To clarify, the authors measured microvessel densities with quantitative morphometry. Left middle cerebral arteries of adult male Sprague-Dawley rats were occluded with intraluminal nylon suture for 4 hours followed by 7, 14, 19, or 30 days of reperfusion. Controls received no surgery or suture occlusion. Changes in microvessel density and macrophage numbers were measured by light microscopic morphometry using semiautomated stereologic methods. Microvessel density increased only in the ischemic margin adjacent to areas of pannecrosis and was always associated with increased numbers of macrophages. Ischemic brain areas without macrophages displayed no vascularity changes compared with normal animals. These data suggest that ischemia-induced microvessels are formed to facilitate macrophage infiltration and removal of necrotic brain.

Vascular endothelial growth factor (VEGF) is currently considered a potential pharmacologic agent for stroke therapy because of its strong neuroprotective and angiogenic capacities. Nonetheless, it is unclear how neuroprotection and angiogenesis by exogenous VEGF are related and whether they are concurrent events. In this study, the authors evaluated by stereology the effect of VEGF on neuronal and vascular volume densities of normal and ischemic brain cortices of adult male Sprague-Dawley rats. Ischemia was induced by a 4-hour occlusion of the middle cerebral artery. Low, intermediate, and high doses of VEGF165 were infused through the internal carotid artery for 7 days by an indwelling osmotic pump. The low and intermediate doses, which did not induce angiogenesis, significantly promoted neuroprotection of ischemic brains and did not damage neurons of normal brains. In contrast, the high dose that induced angiogenesis showed no neuroprotection of ischemic brains and damaged neurons of normal brains. These findings suggest that in vivo neuroprotection of ischemic brains by exogenous VEGF does not necessarily occur simultaneously with angiogenesis. Instead, neuroprotection may be greatly compromised by doses of VEGF capable of inducing angiogenesis. Stroke intervention efforts attempting to induce neuroprotection and angiogenesis concurrently through VEGF monotherapy should be approached with caution.

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It is a tribute to the monumental character of the work published by Key and Retxius in 1876 that there has been little need to present further anatomical reports concerned with the gross and microscopic morphology of the meninges. Subsequent workers have dealt either with broader problems such as the circulation of the cerebrospinal fluid, or with particular aspects of meningeal anatomy such as the perivascular relations. The present authors have considered the latter problem in another communication (Maynard, Schultz and Pease, '57), and this will not be discussed further here, except to call the reader's attention to the excellent review of Woollam and Millen ( '54).The investigators who have concerned themselves primarily with cerebrospinal fluid circulation naturally have made morphological contributions of importance. Of particular significance is the work of Weed ( '17) on the development of the meninges and their spaces. Although it has come to be accepted that the arachnoid effectively isolates the central ne~--vous system and the cerebrospinal fluid from surrounding connective tissue and its fluid spaces, the light microscopist has not been able to characterize cells of this layer very effectively. Their boundaries have been refractory to silver impregnation

Insulated, bipolar stainless steel electrodes were chronically implanted in various regions of the cat brain and the long-term structural changes in the tissue surrounding the electrodes were studied by light and electron microscopy. A sheath surrounded and separated the electrode from normal grey or white matter. A layer of foreign body giant cells of variable thickness was formed adjacent to the electrode. This layer was attenuated in some places so that it was unrecognizable by light microscopy. The bulk of the sheath structure consisted of collagen fibrils, leptomeningeal cells and hypertrophied astrocytes. Areas consisting of modified leptomeningeal cells with long thin processes we designated as spongy areas. These have not been previously reported using the electron microscope. Glycogen bodies were seen in leptomeningeal cells. Astrocytes became greatly enlarged and were more numerous in and around the sheath. Oligodendrocytes contained lamellar bodies, and direct continuity was shown between a lamellar body and an adjacent myelin sheath. Myelin was seen in abnormal sites (around oligodendrocytes and neurons) and in unusual configurations. Neuronal changes near the sheath included whorls and stacks of modified endoplasmic reticulum and the presence of cytoplasmic nucleolus-like bodies. Reactive, regenerative and degenerative axons were observed. Blood vessels were more numerous in the sheath and surrounding tissue than normal. Perivascular spaces were prominent even around capillaries and often plasma cells and monocytes were in these spaces. As compared to normal tissue the extracellular space is noticeably increased. Electrodes passing through ventricles were surrounded with a sheath covered with ependymal cells. This sheath was comparable in structure to the sheath present around the electrode in other locations.

There are different interpretations of tethered cord syndrome (TCS) partly due to difficulty in understanding the concept of this syndrome as a functional disorder not merely based on gross anatomy of congenital anomalies. The essential mechanical factor of cord tethering is that any of the inelastic structures fastening the caudal end of the spinal cord produces traction effects on the lumbosacral cord. The production of such traction is the key to understanding this disorder. In a significant number of patients who present with the typical clinical signs and symptoms of TCS, the diameter of the filum terminale is found within normal limits and the caudal end of the spinal cord is located in the normal position. Therefore, the definition of TCS requires the demonstration that there is a posterior displacement of the conus and filum by MRI, lack of viscoelasticity by the stretch test of the filum during surgery, and fibrous displacement of glial tissue within the filum by histological studies. This is because there is inconsistency from such studies as ultrasonography, MRI and CT myelography, which attempt to establish the presence of a tight filum terminale. A goal of this article is to provide basic understanding of TCS so that clinicians can use the concept of stretch-induced spinal cord dysfunction for proper diagnosis and treatment of this disorder.

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