Early entry of plasma proteins into damaged neurons in brain infarcts

Løberg, E. M.; Hassel, Bjørnar; Fonnum, Frode; Torvik, Ansgar

doi:10.1111/j.1699-0463.1994.tb05233.x

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…Also, significant cell injury or death could not account for epileptogenesis (Fig. 7), although it has been previously shown that vasogenic edema may be associated with accumulation of serum proteins in the cytoplasm of injured neurons (Loberg et al, 1994), followed by cytochrome release and DNA fragmentation (Matz et al, 2001). Although cell loss was not found, we show here robust enhanced GFAP staining restricted to the BBB-disrupted cortex.…”

Section: Discussioncontrasting

confidence: 51%

Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex

Seiffert¹,

Dreier²,

Ivens³

et al. 2004

J. Neurosci.

459

395

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Perturbations in the integrity of the blood-brain barrier have been reported in both humans and animals under numerous pathological conditions. Although the blood-brain barrier prevents the penetration of many blood constituents into the brain extracellular space, the effect of such perturbations on the brain function and their roles in the pathogenesis of cortical diseases are unknown.In this study we established a model for focal disruption of the blood-brain barrier in the rat cortex by direct application of bile salts. Exposure of the cerebral cortex in vivo to bile salts resulted in long-lasting extravasation of serum albumin to the brain extracellular space and was associated with a prominent activation of astrocytes with no inflammatory response or marked cell loss. Using electrophysiological recordings in brain slices we found that a focus of epileptiform discharges developed within 4 -7 d after treatment and could be recorded up to 49 d postoperatively in Ͼ60% of slices from treated animals but only rarely (10%) in sham-operated controls. Epileptiform activity involved both glutamatergic and GABAergic neurotransmission. Epileptiform activity was also induced by direct cortical application of native serum, denatured serum, or albumin-containing solution. In contrast, perfusion with serum-adapted electrolyte solution did not induce abnormal activity, thereby suggesting that the exposure of the serum-devoid brain environment to serum proteins underlies epileptogenesis in the blood-brain barrier-disrupted cortex. Although many neuropathologies entail a compromised bloodbrain barrier, this is the first direct evidence that it may have a role in the pathogenesis of focal cortical epilepsy, a common neurological disease.

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Section: Discussioncontrasting

confidence: 51%

Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex

Seiffert¹,

Dreier²,

Ivens³

et al. 2004

J. Neurosci.

459

395

View full text Add to dashboard Cite

show abstract

“…The wide inter‐individual and interregional variability in the pattern of staining is consistent with this concept, since not only the distribution, but also the specific form of tissue damage could be expected to diverge widely among individuals and regions as the brain dies. Loberg and Torvik have shown in experimental animals that serum protein uptake in damaged neuronal perikarya takes place within minutes of leakage across the blood‐brain barrier, 22 and a similar pattern can be induced by ischemia 39 . Several other serum proteins—IgG, complement C3c—are found in the brain rarely and inconsistently.…”

Section: Discussionmentioning

confidence: 99%

Serum Protein Leakage in Alzheimer's Disease Revisited

Muñoz

Erkinjuntti

Gaytan-Garcia

et al. 1997

Annals of the New York Academy of Sciences

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Leakage of serum proteins into the brain parenchyma has been repeatedly used as evidence of blood-brain barrier (BBB) damage in experimental and human studies. However, there is no consensus in the literature concerning this phenomenon in Alzheimer's disease (AD). We have examined this question by comparing frontal lobe sections in seven groups of patients: Multi-infarct dementia (n = 6), AD with (n = 10) and without (n = 10) infarcts, age-matched controls with (n = 10) and without (n = 10) infarcts, controls with neurodegenerative diseases other than AD, and young controls (n = 10). An additional series compared prospectively followed patients with a diagnosis of either multi-infarct dementia (n = 5) or AD (n = 4). Albumin was detected in white-matter astrocytes in all cases, without significant variation in intensity. In addition, diverse combinations of neurons, astrocytes, and (in AD patients) senile plaques were present in the cerebral cortex in an inconsistent manner. Semiquantitative analysis showed no statistically significant differences among groups. Anti-IgG labeled astrocytes in infarcts only. Complement C3c component was detected in rare amyloid plaques in a minority (15%) of AD cases. Selective labeling of AD-specific lesions in a patchy manner was observed for serum amyloid P. We conclude that there is no immunohistochemical evidence of alteration of the BBB in Alzheimer's disease with or without vascular factors or in old age. Serum amyloid P binds avidly to AD lesions, but our findings are consistent with leakage through the BBB during the agonal or immediate postmortem period. Finally, no specific pattern of abnormality in the BBB was detected in multi-infarct dementia.

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“…We assigned a maximal score of 16 (cortical gray matter: 4.0; cortical white matter: 4.0; hippocampus: 4.0; cerebellum: 4.0) to experimental piglets that could not survive for 5 days due to severe seizures. This was because the minimum time for visible histologic damage to develop is shorter with increasing injury severity, and an increasing number of damaged neurons are visible from 6 to 24 h (Brierley et al, 1971;Løberg et al, 1994). Early evaluation might therefore cause underestimation of the damage.…”

Section: Histologymentioning

confidence: 99%

Cerebral blood volume measurement using near‐infrared time‐resolved spectroscopy and histopathological evaluation after hypoxic‐ischemic insult in newborn piglets

Nakamura

Jinnai

Hamano

et al. 2015

Intl J of Devlp Neuroscience

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The aim of this study was to assess the relationship between the cerebral blood volume (CBV) measured by near-infrared time-resolved spectroscopy (TRS) and pathological change of the brain in a hypoxic-ischemic (HI) piglet model. Twenty-one anesthetized newborn piglets, including three sham controls, were studied. An HI event was induced by low inspired oxygen. CBV was measured using TRS (Hamamatsu TRS-10). Data were collected before, during, and 6h after the insult. CBV was calculated as the change from the end of the insult. The piglets were allowed to recover from anesthesia for 6h after the insult. At the age of 5 days, the brains of the piglets were perfusion-fixed, and histologic evaluations of brain tissue were performed. The extent of histopathological damage was graded in 0.5-unit intervals on a 9-step scale. CBV increments were well correlated with histopathological scores, especially at 1 and 3h after resuscitation. Spearman's rank-correlation coefficients at 1, 3, and 6h after resuscitation in the gray matter were 0.9016, 0.9127, and 0.6907, respectively. We conclude that an increased CBV after HI insult indicates more marked histological brain damage. CBV measurement immediately after resuscitation provides a more precise prediction of the histological outcome.

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Early entry of plasma proteins into damaged neurons in brain infarcts

Cited by 8 publications

References 20 publications

Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex

Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex

Serum Protein Leakage in Alzheimer's Disease Revisited

Cerebral blood volume measurement using near‐infrared time‐resolved spectroscopy and histopathological evaluation after hypoxic‐ischemic insult in newborn piglets

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