Embolized cerebral arteriovenous malformations: a multivariate analysis of 101 excised specimens.

OBJECTIVE: Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens. METHODS: The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980-2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision. RESULTS: A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates. CONCLUSIONS: Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body-type granulomatous inflammation are more common at 1 week and beyond.

Human central nervous system tissue culture: a historical review and examination of recent advances.

Tissue culture has been and continues to be widely used in medical research. Since the beginning of central nervous system (CNS) tissue culture nearly 100 years ago, the scientific community has contributed innumerable protocols and materials leading to the current wide variety of culture systems. While nonhuman cultures have traditionally been more widely used, interest in human CNS tissue culture techniques has accelerated since the middle of the last century. This has been fueled largely by the desire to model human physiology and disease in vitro with human cells. We review the history of human CNS tissue culture summarizing advances that have led to the current breadth of options available. The review addresses tissue sources, culture initiation, formats, culture ware, media, supplements and substrates, and maintenance. All of these variables have been influential in the development of culturing options and the optimization of culture survival and propagation.

Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity.

BACKGROUND: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. METHODS: Human CNS cultures were derived from 16-18 week gestation post-mortem fetal brain. Cultures were incubated with 400 microM ascorbate-2-O-phosphate (Asc-p) or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2) and astrocytic (GFAP) structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM). RESULTS: Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. CONCLUSIONS: Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures.

Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia.

HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120). In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

HIV-1/AIDS neuropathology in a Canadian teaching centre.

BACKGROUND: The nervous system is a major target of HIV-1 infection and site of many complications of AIDS. Most of our knowledge pertaining to the range and frequency of neuropathology in HIV-1/AIDS is from large centres outside Canada in different social and health care settings. The goal of the present study was to describe HIV-1/AIDS-associated neuropathology before and during the era of highly active antiretroviral therapy at a Canadian teaching centre. METHODS: The records of the Department of Pathology, London Health Sciences Centre were electronically searched for cases of HIV-1/AIDS that came to postmortem examination since 1985. The clinical records and pathological materials were reviewed. RESULTS: Sixteen autopsies of HIV-1/AIDS were identified. All patients were male. Fourteen contracted HIV-1 through high risk homosexual activity, one through the transfusion of blood products and one through intravenous drug use. Three patients (19%) had pre-mortem evidence of HIV-1 associated dementia. At autopsy, 12 of the 16 cases had neuropathological findings and the most common diagnoses were HIV-1 encephalitis, progressive multifocal leukoencephalopathy, toxoplasmosis, and primary CNS lymphoma. CONCLUSIONS: High risk homosexual activity was a more prominent factor in acquiring AIDS in cases coming to postmortem examination compared with previous reports from most larger urban centres outside Canada where injection drug use and high risk heterosexual activity factored prominently. The incidence of HIV-1 associated dementia was similar to that reported previously. This study confirms the heavy burden and wide spectrum of disease experienced by the nervous system in HIV-1/AIDS.

AZT myopathy and HIV-1 polymyositis: one disease or two?

PURPOSE: This paper discusses the association between inflammatory and mitochondrial pathologies in patients with HIV-1/AIDS treated with zidovudine (AZT). METHODS: We present the clinical and pathological details of a 52-year-old HIV-1 positive male who presented with progressive muscle weakness. We also review the current literature and address the debated pathogenesis of the inflammatory pathology. RESULTS: Muscle biopsy revealed evidence of both HIV-1 polymyositis and AZT myopathy. Six months after initiation of corticosteroid therapy and discontinuation of AZT, the patient's symptoms had greatly improved. The biopsy was repeated to show that both pathologies had resolved. CONCLUSIONS: The perceived overlap in the pathological spectra of HIV-1 polymyositis and AZT myopathy has produced some debate on causation and treatment. Unfortunately, there have been very few reports where a repeat biopsy following a drug washout period confirmed resolution of the pathology. Furthermore, affected patients have not been treated in a uniform fashion. Whether this represents one disease or two remains uncertain. The clinical relevance of this issue lies in the potential for harm from the unnecessary use of corticosteroids. This question may be best addressed by a randomized clinical trial.