Neurotoxicity of Serum Components, Comparison Between CA1 and Striatum

Kadota, Eiji; Nonaka, Kiyoko; Karasuno, M.; Nishi, Katsuhide; Teramura, Kazuhiro; Hashimoto, Shigeo

doi:10.1007/978-3-7091-6837-0_43

Cited by 8 publications

(6 citation statements)

References 5 publications

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“…To our knowledge, plasma has not been examined previously for its direct neurotoxic effects or its ability to modulate excitotoxic damage. However, autologous serum and rat albumin have been injected into the rat brain and neurotoxicity was observed (Hassel et al, 1994;Kadota et al, 1997). The difference in results between these studies and ours could be caused by a difference in protocols.…”

Section: Discussionmentioning

confidence: 64%

“…The difference in results between these studies and ours could be caused by a difference in protocols. Whereas we infused plasma at a rate of 0.5 l/hr for 4 d, the previous studies injected a 25 l volume of serum or albumin into the rat brain in a shorter time (Hassel et al, 1994;Kadota et al, 1997). It is possible that the large volume injection coupled with increased fluid extravasation attributable to protein osmotic effects could have contributed to edema-mediated neuronal death in those studies.…”

Section: Discussionmentioning

confidence: 98%

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Neuronal Death and Blood–Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes

et al. 1999

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Neuronal damage in the CNS after excitotoxic injury is correlated with blood-brain barrier (BBB) breakdown. We have used a glutamate analog injection model and genetically altered mice to investigate the relationship between these two processes in the hippocampus. Our results show that BBB dysfunction occurs too late to initiate neurodegeneration. In addition, plasma infused directly into the hippocampus is not toxic and does not affect excitotoxin-induced neuronal death. To test plasma protein recruitment in neuronal degeneration, we used plasminogen-deficient (plg(-/-)) mice, which are resistant to excitotoxin-induced degeneration. Plasminogen is produced in the hippocampus and is also present at high levels in plasma, allowing us to determine the contribution of each source to cell death. Intrahippocampal delivery of plasminogen to plg(-/-) mice restored degeneration to wild-type levels, but intravenous delivery of plasminogen did not. Finally, although the neurons in plg(-/-) mice do not die after excitotoxin injection, BBB breakdown occurs to a similar extent as in wild-type mice, indicating that neuronal death is not necessary for BBB breakdown. These results indicate that excitotoxin-induced neuronal death and BBB breakdown are separable events in the hippocampus.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 98%

Neuronal Death and Blood–Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes

et al. 1999

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“…31 In addition to potential effects on the transmigratory ability of inflammatory cells, altered BBB permeability may allow potentially toxic serum proteins, including thrombin, to enter the CNS. [52][53][54][55] It is interesting that thrombin has been shown to affect dendritic arborization, 54 which is reduced in association with HIVD. 56 Although similarly speculative, it is also possible that MMPs may have more direct effects on brain-derived cells.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia

et al. 1999

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Pathological evidence suggests that alterations of the blood-brain barrier (BBB) may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). Increased BBB permeability could contribute to the development of dementia by facilitating the entry of activated and infected monocytes, as well as potentially toxic serum proteins, into the central nervous system. One mechanism by which BBB permeability may be altered is through increased activity of select matrix metalloproteinases (MMPs). In the present study, we examined the possibility that MMPs that target critical BBB proteins, including laminin, entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of patients with HIVD. We also examined the possibility that such MMPs could be produced by brain-derived cells, and that MMP production by these cells might be increased by tumor necrosis factor-␣, an inflammatory cytokine that is produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using western blot and enzyme-linked immunosorbent assay, we observed that CSF levels of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, through the use of gelatin substrate zymography, a sensitive functional assay for MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF from either nondemented seropositive (2/11) or seronegative (0/11) controls. Although the presence of MMPs in the serum could contribute to elevated levels in the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that such release is increased after their stimulation with tumor necrosis factor-␣. Together, these results suggest that elevated CSF levels of select MMPs may reflect immune activation within the central nervous system. They also suggest that further studies may be warranted to determine whether these proteins may play a role in the development of symptomatic neurological disease.

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“…Furthermore, endothelial dysfunction contributes to BBB breakdown, resulting in the exudation of serum components into nervous tissue (Farooque et al, 1992). This may trigger apoptotic neuronal death and enhance superoxide production in microglia following vasogenic edema (Kadota et al, 1997;Si et al, 1997;Murakami et al, 1998). At longer survival periods, extensive extravasation of serum albumin has been described (Farooque et al, 1992).…”

Section: Introductionmentioning

confidence: 97%

“…Zones of ischemic brain tissue are always present around traumatic lesions and may persist for weeks or months due to astrocytic swelling and microvascular compression (Bullock et al, 1992a). Perivascular hemorrhage often exists in contusion (Shreiber et al, 1999), and glutamate may be released from areas of hemorrhage and their surround, further injuring neurons (Bullock et al, 1992bBaker et al, 1993;Zauner and Bullock, 1995;Kadota et al, 1997;Matsushita et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Analysis of Microvascular Alterations in Traumatic Brain Injury by Endothelial Barrier Antigen Immunohistochemistry

Lin

Ginsberg

Zhao

et al. 2001

Journal of Neurotrauma

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Endothelial barrier antigen (EBA) is a protein triplet located in the plasma membrane of microvascular endothelium and selectively expressed in the normal nervous system. In this study, microvascular alterations following traumatic brain injury were studied using EBA immunohistochemistry. Anesthetized, physiologically regulated, normothermic Sprague-Dawley rats received moderate (1.5-2.0 atm) parieto-occipital parasagittal fluid-percussion traumatic brain injury (TBI). Control rats were subjected to similar anesthesia and physiological monitoring. Seven days after operative procedures, brains were perfusion-fixed, and coronal sections were reacted for EBA immunohistochemistry using a monoclonal antibody to rat EBA. Selected sections were reacted for isolectin B4 histochemistry. Computerized image analysis was used to compute numbers of EBA-immunopositive vascular profiles and mean vascular profile areas. In control brains, virtually all brain microvessels were clearly and positively immunostained, and antibody binding was specific for blood vessels. In rats with TBI, EBA immunoreactivity was greatly reduced in the zone of cortical contusion. Within the core contusion, fractional areas occupied by vascular profiles were markedly reduced (on average, by 57%), vascular profile counts were diminished, and lectin histochemistry revealed a robust inflammatory response with abundant macrophages. Taken together, these findings were thought to indicate frank microvascular destruction. At adjacent peri-contusional sites, the intensity of EBA immunostaining was also diminished; and vascular profile counts were reduced at adjacent cortical sites and homologous contralateral sites. The latter findings were interpreted as sublethal microvascular alterations possibly related to cerebral edema. The present results confirm that EBA is a specific immunohistochemical marker of normal central nervous system microvessels; that it is suitable for use in formaldehyde-fixed material; and that it is useful in quantitatively assessing microvascular alterations observed at contusional, peri-contusional and more remote sites following traumatic brain injury.

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Neurotoxicity of Serum Components, Comparison Between CA1 and Striatum

Cited by 8 publications

References 5 publications

Neuronal Death and Blood–Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes

Neuronal Death and Blood–Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes

Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia

Quantitative Analysis of Microvascular Alterations in Traumatic Brain Injury by Endothelial Barrier Antigen Immunohistochemistry

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