Destruction Of Brain Tissue Research Articles

Expression of CD80 and CD86 in the brain of Lewis rats after induction of stroke

Introduction: Cerebral ischemia induces brain tissue destruction. While the cascades leading to cellular death have been well investigated, the immune response following cerebral stroke has not been investigated in detail to date. This immune response is characterised by infiltration of lymphocytes into the brain lesion.

Virus and host factors that mediate the clinical and behavioral signs of experimental herpetic encephalitis. A short auto-review.

Experimental models that mimic the clinical syndrome of human viral encephalitis and represent HSV-1 neurotropism were utilized to investigate neuro-pharmacologic changes mediating clinical and behavioral manifestations of encephalitic infection of the central nervous system with HSV-1-induced rapid activation of the hypothalamic--pituitary--adrenocortical (HPA) axis and production of brain derived interleukin-1 (IL-1) and prostaglandin E2 (PG-E2), independently of viral replication. HSV-1 infection induced clinical signs of fever, motor hyperactivity and aggressive behavior. These manifestations were dependent on a permissive action of circulating glucocorticoids and not related to the degree of viral replication in the brain. Hyperthermia and HPA axis activation were also specifically dependent on HSV-1-induced brain IL-1 and PG-E2. The chronic neurological sequel or fatal outcome of HSV-1 encephalitis may be due to viral replication and brain tissue destruction, which are dependent on virus encoded virulence genes. In contrast, the clinical and behavioral signs in the acute phase are a result of activation of neurochemical systems, including cytokines, prostaglandinds and catecholamines. Circulating glucocorticoids play an essential role in mediating the physiologic actions of HSV-1-induced brain products and the clinical syndrome of encephalitis.

S100β and NSE: Stroke surrogate signals or natal neural noise?

S100β and NSE: Stroke surrogate signals or natal neural noise?

Perioperative head injury management in the multiply injured trauma patient.

Traumatic brain injury (TBI) in the multiply injured patient can be challenging to manage for trauma surgeons, neurosurgeons, and anesthesiologists due to the competing priorities of the diagnostic workup and treatment ofbrain injuries versus systemic injuries. TBI is the leading cause of death in trauma victims, accounting for approximately half of all trauma-related deaths. 1 Destruction of brain tissue occurs in two phases: the primary injury, which involves direct tissue damage at the time of the inciting event, and the subsequent secondary injury, which occurs due to ischemia, causing calcium ion influx and free radical accumulation. Primary injury is considered irreversible, and therefore therapy is directed toward minimizing the secondary brain injury by optimizing cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) and by aggressive treatment of intracranial hypertension.

Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes

Highly reactive gaseous free radical nitric oxide (NO), generated by astrocytes and infiltrating macrophages is implicated in inflammatory destruction of brain tissue, including that occurring in multiple sclerosis. Therefore, the influence of immunosuppressive drug leflunomide on inducible nitric oxide synthase (iNOS)-dependent NO production in rat astrocytes and macrophages was investigated. Under the same cultivating conditions, leflunomide’s active metabolite A77 1726 caused a dose-dependent decrease of NO production in IFN-γ+LPS-stimulated primary astrocytes, but not in macrophages. While A77 1726 did not alter iNOS enzymatic activity, it markedly suppressed IFN-γ+LPS-triggered expression of iNOS mRNA in astrocytes. In the presence of transcription inhibitor actinomycin D, A77 1726 failed to inhibit astrocyte NO production, suggesting transcriptional regulation of iNOS by leflunomide. This assumption was further supported by the ability of A77 1726 to inhibit IFN-γ+LPS-induced expression of mRNA for an important iNOS transcription factor IRF-1. PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MAPKK/MEK), but not genistein, an unselective protein tyrosine kinase inhibitor, completely mimicked cell type-specific inhibition of NO synthesis by A77 1726. Therefore, previously described inhibition of MEK/MAP pathway by leflunomide could present a possible mechanism for A77 1726-mediated suppression of iNOS activation in astrocytes. Accordingly to results obtained with primary astrocytes, both A77 1726 and PD98059 significantly reduced IFN-γ+LPS-induced NO synthesis in the cultures of rat astrocytoma cell line C6. The ability to suppress iNOS induction in astrocytes supports potential use of leflunomide in the treatment of multiple sclerosis and other NO-dependent inflammatory brain disorders.

P24Fetal porencephaly as a rare complication of epignathus occluding blood flow in the internal carotid artery

BackgroundEpignathus is a rare benign congenital teratoma of the hard palate. Some of these tumors protrude bidirectionally involving pharyngeal as well as intracranial structures. The poor prognosis of the affected fetuses is due to consecutive airway obstruction and destruction of brain tissue. We report an unusual case of epignathus leading to compression of the internal carotid artery with subsequent porencephaly.In a 27‐year‐old gravida 1 at 25 weeks gestational age with polyhydramnios, ultrasound examination demonstrated extensive epignathus with displacement of adjacent structures, hydrocephaly and porencephaly. Neither brainstem nor cerebellum could be clearly identified. A steal effect was excluded as low tumor vascularisation and high resistance indices of the supplying vessels was demonstrated, therefore porencephaly was suspected to be caused by vascular compromise. Amniocentesis revealed a normal karyotype. The parents elected to terminate the pregnancy. Autopsy results were confirmatory. An immature teratoma of the hard palate measuring 95 × 42 × 32 mm compressing the left internal carotid artery was demonstrated, leading to colliquation necrosis of the left hemisphere. Additionally displacement of brainstem and infiltration of cerebellum led to cerebrospinal fluid block and consecutive hydrocephalus.ConclusionOnly few reports exist on the prenatal diagnosis of epignathus. We report the first case of epignathus causing extensive brain damage by vascular compromise.

Ultrasonic contact microprobe: experimental results.

At the Department of Neurosurgery, School of Medicine, University of Zagreb, the original ultrasonic contact microprobe (UCM) was designed. The efficacy of the instrument was tested on 120 brains of Wistar strain rats. The authors have been investigating the possibility of transferring high-energy ultrasound through the titanium wire probe of the device and the efficacy of UCM in controlled punctiform destruction of brain tissue. Light and electron microscope assessed the lesions made in the brains of experimental rats. Histological findings in the preparations showed the zone of thermal injuries from 100 to 200 microm and the zone of ultrastructural changes from 200 to 300 microm, indicating the sparing effect of the microprobe with regard to the adjacent neurovascular structures. The small dimensions of the ultrasonic contact microprobe (1.6 mm) enable its introduction through the operating canal of a ventriculoscope. Further research is expected to show the efficacy of the ultrasonic contact microprobe in endoscopic neurosurgery.

Brain injury after gunshot wounding: morphometric analysis of cell destruction caused by temporary cavitation.

In addition to the primary destruction of brain tissue readily visible at autopsy (permanent track), gunshot wounding to the brain creates a pulsating temporary cavity due to radial expansion along the bullet's track. To determine the maximum extent of this temporary cavitation in brains of victims of gunshots from weapons with low muzzle velocity, we carried out morphometric studies on 20 cases of death from gunshot wounding to the head from bullets with a muzzle energy <500 J and a survival time of <90 min. The brains were fixed in formalin, examine macroscopically and microscopically, and subjected to morphometric analyses. Surrounding the permanent track, a narrow mantle-like zone of astrocyte destruction was found within an area of hemorrhagic extravasation. Axons near the permanent track had been broken into tiny fragments. The axonal damage lessened with increasing distance from the permanent track, although axons continued to be fragmented and to exhibit varicose changes and clumping until assuming their normal structure beyond 18 mm. Nerve cells were extremely shrunken close to the permanent track but gradually took on their normal shape with increasing distance. We also assessed the loss of glial fibrillary acid protein expression by astrocytes in the white matter, the extent of traumatic bleeding, and damage to axons and neurons as measured radially from the permanent track. Axonal and neuronal damage were found to extend about 18 mm radially from the permanent track, tapering gradually along the track from entry point to exit point. The destruction was probably produced by the temporary cavitation and accords with theoretical considerations and experimental observations.

Inflammatory molecule release by β-amyloid-treated T98G astrocytoma cells: role of prostaglandins and modulation by paracetamol

Deposition of β-amyloid in the brain triggers an inflammatory response which accompanies the neuropathologic events of Alzheimer's disease and contributes to the destruction of brain tissue. The present study shows that β-amyloid can stimulate human astrocytoma cells (T98G) to secrete the proinflammatory factors interleukin-6 and prostaglandins. Furthermore, prostaglandins can stimulate T98G to secrete interleukin-6, which in turn triggers the formation of additional prostaglandins. Prostaglandins are, therefore, a key element in the induction and maintenance of a state of chronic inflammation in the brain which may exacerbate the fundamental pathology in Alzheimer patients. Paracetamol (0.01–1000 μM), an unusual analgesic/antipyretic drug which acts preferentially by reducing prostaglandin production within the central nervous system, and indomethacin (0.001–10 μM) caused a clear dose-dependent reduction of prostaglandin E 2 production by stimulated T98G cells whereas interleukin-6 release was not affected. These data provide further evidence of the involvement of non-steroidal anti-inflammatory drugs in the inflammatory processes that can be generated by glial cells in intact brain.

Interactions between Astrocytes and Oligodendroglia in Human and Experimental Creutzfeldt–Jakob Disease and Scrapie

We report here a rare interaction between reactive astrocytes and oligodendrocytes, first detected in a brain biopsy of human Creutzfeldt–Jakob disease (CJD) and then in experimental CJD in mice and in two models (263K and 22CH) of scrapie in hamsters. In human CJD brain biopsy, low-power electron microscopy revealed numerous examples of astrocytes and oligodendroglial cells in close apposition. At higher magnification, both types of cells were occasionally connected by adhesive plaque junctions (attenuated desmosomes). More complex structures were also seen. Astrocytic cytoplasm was penetrated by oligodendroglial processes or oligodendroglial cells were completely surrounded by astrocytic processes. An analogous phenomenon was identified in the brains of CJD-infected mice and in two models of scrapie-infected hamsters. In the CJD brain biopsy and in brain specimens from CJD-infected mice and scrapie-infected hamsters, GFAP-immunoreactive hypertrophic astrocytes were readily identified, particularly in those areas where the tissue damage was the most extensive. Oligodendrocytes frequently surrounded hypertrophic astrocytic processes or cell bodies and remained unstained in GFAP preparation. The significance of the interactions between astrocytes and oligodendrocytes is unclear at the present time. As in MS and other brain pathologies in which it has been studied, this interaction is not associated with a reaction toward any infectious pathogen but it may be an early cellular event that triggers further brain tissue destruction.

Immune-mediated brain atrophy. CD8+ T cells contribute to tissue destruction during borna disease.

Borna disease (BD) is a virus-induced immunopathologic disease of the central nervous system in a variety of species from birds to primates and probably in humans. Severe inflammatory reactions lead to tissue destruction and finally to cortical brain atrophy. After experimental infection of the rat, intraparenchymal CD8+ T cells, MHC class I Ags on Borna disease virus (BDV)-infected neurons, and numerous nerve cell lesions were present. Treatment of BDV-infected rats with the mAb OX-8 directed against CD8+ cells inhibited the immunopathologic reactions and reduced MHC class I Ag expression. Neuronal lesions were minimal and no loss of brain substance could be observed. Because BDV has no acute cytopathic effects, we provide evidence that the presence of CD8+ T cells within the brain parenchyma and the expression of MHC class I Ags on neurons play a major role for immunopathologic brain tissue destruction and virus-infected neurons in vivo can be destroyed by T cell-mediated cytotoxicity.

Transfection of glioma cells with the neural-cell adhesion molecule NCAM: effect on glioma-cell invasion and growth in vivo.

The tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140-kDa isoform of the neural-cell adhesion molecule, NCAM. After s.c. injection, the NCAM-transfected cells showed a slower growth rate than the parent cell line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM-transfected cells, all animals developed neurological symptoms within 13-16 days. However, the tumors showed different growth characteristics. The NCAM-transfected BT4Cn cells were localized in the region of the injection site, with a sharply demarcated border between the tumor and brain tissue. In contrast, the parental cell line showed single-cell infiltration and more pronounced destruction of normal brain tissue. Using a 51Cr-release assay, spleen cells from rats transplanted with BT4Cn tumor cells generally showed a lower cytotoxic response than the spleen cells from rats transplanted with the transfected variants of BT4Cn cells, indicating that the transfection procedure in itself mediated an activation of the immune system. The present data suggest that NCAM may influence the malignant behavior of rat glioma cells in vivo.

Nerve growth factor protects against herpes simplex virus type 1 neurotoxicity in the rat striatum.

To determine the effect of nerve growth factor (NGF) on the neurotoxicity of herpes simplex virus type 1 (HSV-1) in vivo, direct intrastriatal injection of HSV-1 in rats was followed by continuous intracerebral infusion of NGF or vehicle solution for 7 days. The mean volume of HSV-1-mediated brain tissue destruction in NGF-treated animals was significantly smaller than that in vehicle-treated animals at 1 week. Immunohistochemical staining for HSV-1 confirmed the presence of cells harboring the virus at the primary site of injection and at secondary sites of distant spread, with no significant difference in HSV-1 distribution between NGF- and vehicle-treated animals. We conclude that intrastriatal infusion of NGF locally protects against HSV-1-mediated neurolysis, but does not affect HSV-1 dissemination in the brain.

Interaction between human medulloblastomas and foetal rat brain aggregates in vitro.

The invasiveness of three medulloblastoma permanent cell lines (D-283, D-341, and DAOY), a human medulloblastoma biopsy, and in addition, a human rhabdomyosarcoma permanent cell line (TE-671), which previously had been regarded as a human medulloblastoma, was studied in an organ co-culture assay. All the four cell lines and the biopsy were co-cultured with normal rat brain cell aggregates for up to six days in vitro. The medulloblastoma biopsy, the D-283 and the D-341 cells invaded the brain tissue by diffuse single cell infiltration. The medulloblastoma cell line (DAOY) showed an invasive pattern similar to that observed earlier for most glioblastoma cell lines. This was characterized by massive cell replacement and destruction of normal brain tissue. The rhabdomyosarcoma cell line (TE-671) presented a solid invasive pattern with a fairly well defined border between normal brain and tumour tissue. Thus, the organ co-culture assay system in vitro seems to mimic several aspects of the in situ invasive behaviour of medulloblastomas. It may, therefore, provide new perspectives for pretreatment investigations with chemotherapy and radiotherapy of these malignancies.

Severe outcome of brain perfusion failure: A pre-hydranencephalic state?

Four children surviving severe hypoxic-ischemic brain damage showed subtotal destruction of the cerebral hemispheres, with partial preservation of some infratentorial and supratentorial brain structures. True multicystic encephalopathy features were identified in two cases on CT scanning. The other patients showed more pronounced brain tissue destruction, with overall malacia of the hemispheres. An echographic study demonstrated that the brain damage occurred progressively, within about one month, and was preceded by oedema, white matter malacia and cavitation. The role of the compensatory mechanisms responsible for preservation of structures supplied by the vertebral-basilar circle is discussed. The authors suggest that the observed outcome could be considered a stage immediately preceding the most severe damage represented by hydranencephaly.

Photodynamic therapy of brain tumours — post-operative “field fractionation”

Malignant primary cerebral tumours account for 3% of the cancer burden and constitute the most common solid tumour in the paediatric age group. In spite of the advances in the surgical treatment, radiation therapy and chemotherapy of these tumours, the prognosis remains very poor. Patients with glioblastoma multiforme, the most common primary cerebral glioma, have a median survival of less than 1 year and a 2 year survival rate of less than 20%. Malignant primary cerebral gliomas cause disability and death as the consequence of local effects. Their invasion and destruction of brain tissue results in neurological disability and the associated increase in intracranial pressure eventually leads to coma and death. Most malignant primary cerebral tumours do not metastasize. Therefore, these tumours represent an excellent example of a highly malignant solid tumour where local tumour control should be of survival value. However, patients with malignant glial brain tumours tend to present clinically with sizable tumours. In a series of 100 consecutive patients with malignant cerebral astrocytic tumours, computed tomography (CT) scan assessment showed the median tumour mass to be 35 g (not including tumour-associated cerebral oedema) [l]. This mass is within two or three doublings of the lethal mass of 100 g. The penetration depth of 630 nm light in brain tumour tissue in vivo is limited to approximately 3 mm [2, 31; the killing distance might thus be estimated to be 8-12 mm. By assuming a spherical geometry, the mass of tissue destroyed with a 1 cm killing radius is estimated to be only 4 g when a point source is used for interstitial photoillumination. A diffusion fibre with a 2 cm cylindrical tip might destroy 6-10 g of tumour tissue if the killing radius is 1 cm. By creating a spherical cavity with a radius of 2 cm within the solid tumour by surgical means and then using intracavitary photoillumination with a 1 cm killing radius, a much larger tumour mass of 80 g of tissue could be destroyed. Thus a combination of intraoperative intracavitsry photoillumination and multiple interstitially placed diffusion fibres may result in a substantial volume of tissue photoillumination and destruction.

Interaction between human brain tumour biopsies and fetal rat brain tissue in vitro

The invasiveness of human intracranial tumours was studied in an organ culture system. Biopsies from six glioblastomas, four astrocytomas, two mixed gliomas, one ependymoma, four meningiomas and two carcinoma metastases were cut into fragments of 0.5 mm diameter, and placed in agar overlay tissue culture. The tumour specimens formed spheroids which were co-cultured with cell aggregates or fragments from fetal rat brain for up to 10 days in vitro. The invasiveness of the glioblastoma spheroids was characterised by a gradual destruction of normal brain tissue by tumour cells, followed by replacement of normal tissue by these cells. Co-cultures from two glioblastomas showed lesions in the normal brain tissue in areas removed from the tumour cells. Tumour spheroids from four glioblastomas totally destroyed the normal brain tissue without any change in the original tumour spheroid configuration. The low-grade gliomas were less invasive than the glioblastomas. The meningiomas and the metastases were non-invasive. This organ culture assay appeared to reflect the in situ invasive behaviour of the brain tumours examined. It is suggested that it may be used for evaluating the aggressiveness of individual brain tumours with the specific aim of correlating clinical data with the biological character of the tumour.

Computer-assisted analysis of behavior-brain damage relationships

Experimental destruction of subcortical brain tissue by electrolytic, radio frequency, or excitotoxin lesions is commonly used in the study of the neural control of behavior. Relating variability in the locus and extent of brain damage to lesion-produced variability in behavior is essential to a complete analysis of the behavioral effects of brain damage. We describe the use of commercially available computer accessories and software for measuring the area of irregular polygons to accurately and rapidly estimate the amount of damage to any of a number of brain structures included within an area of experimental destruction. We then describe the use of statistical programs for correlation and multiple regression in calculating relationships between damage to particular structures and behavior. As an example, we show that excitotoxin (and presumably axon-sparing) lesions of lateral hypothalamic tissue adjacent to the caudal zona incerta virtually eliminate male sexual behavior in rats. The use of multiple regression analysis, in conjunction with procedures for calculating destruction to different brain regions, provides a way of correlating brain damage and behavior that has widespread application in studies of the behavioral effects of brain lesions.

The Psychology of Microcephalics

… Nature herself sometimes conducts experiments that help to shed light on many obscure areas of psychology. For example, we all know the great importance that observations of patients with a lesion of the insular, or central, lobe and contiguous parts of the frontal and temporal lobes have had in clarifying the act of human speech. Many properties of human memory have also become known to us from observations of patients. Finally, the universally acknowledged hypothesis that the activity of the mind depends on the activity of the brain is clearly demonstrated in psychiatric practice in cases in which mental life declines concomitantly with destruction of brain tissue. These things make mental anomalies scientifically interesting not only for the specialist but also for psychologists in general, and attentive study of the symptoms of mental disorders can unquestionably be of great benefit to professional psychologists even at the purely theoretical level. From this standpoint, people whose abnormal physical development has given them an insufficiently developed brain and, hence, an undeveloped or underdeveloped mental life are of considerable, obvious interest for psychologists. These people are designated idiots, or congenitally mentally retarded. Different aspects of their mental life present the most varied levels of development, and thus furnish rich material for study of the laws of mental life in the normal, healthy, human being as well.

Correlation of admission fibrin degradation products with outcome and respiratory failure in patients with severe head injury.

It has been suggested that concentrations of fibrin degradation products (FDPs) after head injury reflect the extent of brain tissue destruction. In addition, elevated FDP concentrations have been associated with the development of the adult respiratory distress syndrome (ARDS). Coagulation variables, including a FDP screen, were measured on the admission of 33 patients with severe closed head injury (Glasgow coma score 8 or less) to define the prognostic value of FDP concentrations. A Glasgow outcome score was assigned to each patient 6 months after injury, and those patients with higher FDP concentrations had poorer functional outcomes. This correlation of outcome with admission FDP concentration was statistically significant, as was the correlation between outcome and the admission Glasgow coma score. Of 22 patients with FDP concentrations of less than 64 micrograms/ml, only 1 developed early respiratory failure, whereas 9 of 11 patients with FDP concentrations of 64 micrograms/ml or more developed ARDS. These findings were not affected by the presence of multiple system trauma. FDP concentrations seem to have prognostic value similar to the Glasgow coma score and seem to identify those patients with head injury who are at high risk for ARDS.