Neuroprotective Effect of Chronic Intracranial Toxoplasma gondii Infection in a Mouse Cerebral Ischemia Model.

Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade various organs in the host body, including the central nervous system. Chronic intracranial T. gondii is known to be associated with neuroprotection against neurodegenerative diseases through interaction with host brain cells in various ways. The present study investigated the neuroprotective effects of chronic T. gondii infection in mice with cerebral ischemia experimentally produced by middle cerebral artery occlusion (MCAO) surgery. The neurobehavioral effects of cerebral ischemia were assessed by measurement of Garcia score and Rotarod behavior tests. The volume of brain ischemia was measured by triphenyltetrazolium chloride staining. The expression levels of related genes and proteins were determined. After cerebral ischemia, corrected infarction volume was significantly reduced in T. gondii infected mice, and their neurobehavioral function was significantly better than that of the uninfection control group. Chronic T. gondii infection induced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in the brain before MCAO. T. gondii infection also increased the expression of vascular endothelial growth factor after the cerebral ischemia. It is suggested that chronic intracerebral infection of T. gondii may be a potential preconditioning strategy to reduce neural deficits associated with cerebral ischemia and induce brain ischemic tolerance through the regulation of HIF-1α expression.

Incorporating Stroke Severity Into Hospital Measures of 30-Day Mortality After Ischemic Stroke Hospitalization.

BACKGROUND AND PURPOSE: The Centers for Medicare & Medicaid Services publicly reports a hospital-level stroke mortality measure that lacks stroke severity risk adjustment. Our objective was to describe novel measures of stroke mortality suitable for public reporting that incorporate stroke severity into risk adjustment. METHODS: We linked data from the American Heart Association/American Stroke Association Get With The Guidelines-Stroke registry with Medicare fee-for-service claims data to develop the measures. We used logistic regression for variable selection in risk model development. We developed 3 risk-standardized mortality models for patients with acute ischemic stroke, all of which include the National Institutes of Health Stroke Scale score: one that includes other risk variables derived only from claims data (claims model); one that includes other risk variables derived from claims and clinical variables that could be obtained from electronic health record data (hybrid model); and one that includes other risk variables that could be derived only from electronic health record data (electronic health record model). RESULTS: The cohort used to develop and validate the risk models consisted of 188 975 hospital admissions at 1511 hospitals. The claims, hybrid, and electronic health record risk models included 20, 21, and 9 risk-adjustment variables, respectively; the C statistics were 0.81, 0.82, and 0.79, respectively (as compared with the current publicly reported model C statistic of 0.75); the risk-standardized mortality rates ranged from 10.7% to 19.0%, 10.7% to 19.1%, and 10.8% to 20.3%, respectively; the median risk-standardized mortality rate was 14.5% for all measures; and the odds of mortality for a high-mortality hospital (+1 SD) were 1.51, 1.52, and 1.52 times those for a low-mortality hospital (-1 SD), respectively. CONCLUSIONS: We developed 3 quality measures that demonstrate better discrimination than the Centers for Medicare & Medicaid Services' existing stroke mortality measure, adjust for stroke severity, and could be implemented in a variety of settings.

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive. In this review, several alternative approaches recently developed to facilitate the comparison of specific parameters between fatal, non-fatal cerebral malaria and uncomplicated malaria patients are described, as well as their limitations. The emergence of neuroimaging as a revolutionary tool in identifying critical structural and functional modifications of the brain during cerebral malaria is discussed and highly promising areas of clinical research using magnetic resonance imaging are highlighted.

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

Stroke in asymptomatic Trypanosoma cruzi-infected patients.

BACKGROUND: The knowledge about the natural history of stroke in Chagas disease is incomplete. METHODS: Vascular risk factors and stroke subtypes of asymptomatic Trypanosoma cruzi-infected patients with no clinical evidence of heart failure were assessed. They were compared with chronic chagasic cardiomyopathy patients who suffered a stroke and with a control group of 60 T. cruzi-noninfected stroke patients. Eighty-six consecutive chagasic stroke patients (mean age: 57.4 years; 64% females) were studied. RESULTS: 38.4% of chagasic stroke patients had asymptomatic T. cruzi infection. Smoking was more frequent in asymptomatic chagasic stroke patients (21.2 vs. 5.7%; p = 0.04). Prevalence of hypertension, diabetes and prior stroke was similar in both groups. Small-vessel infarction (15.6 vs. 3.8%) and large-vessel atherosclerosis (9.4 vs. 3.8%) were significantly more frequent in asymptomatic than in symptomatic T. cruzi-infected stroke patients (p = 0.001). Nevertheless, their frequency was even higher in T. cruzi-noninfected stroke patients (36.7 and 13.3%, respectively). Apical aneurysm (27.3%), left atrial dilatation (12.1%), left ventricle hypokinesia (9.4%) and right bundle branch block (36.4%) were also detected in asymptomatic T. cruzi-infected stroke patients. CONCLUSIONS: Ischemic stroke may be the first manifestation of Chagas disease in asymptomatic patients with mild left ventricle dysfunction. Other noncardioembolic stroke subtypes can occur in asymptomatic T. cruzi-infected patients.

Morphological assessment of the cerebroprotective action of lanthanum acetate in chronic cerebral ischemia in rats.

The aim of the present work was to perform a morphological assessment of the cerebroprotective action of lanthanum acetate in chronic cerebral ischemia in rats. Chronic ischemia was produced in Wistar rats (weighing 160-180 g) by ligation of both common carotid arteries. Ischemic lesions were corrected by intragastric lanthanum acetate (3 mg/kg per day) throughout the experimental period. Ischemic damage to the cortex was assessed morphometrically on histological sections stained by the Nissl method. Lanthanum acetate was found to suppress the development of ischemic neuron damage in the cerebral cortex, with reductions in the numbers of hyperchromic neurons, cells with focal chromatolysis, and ghost cells, as well as an increase in the number of normochromic cells as compared with controls.

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii.

To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFNgamma). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFNgamma brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia.

Left ventricular hydatid cyst presenting with acute ischemic stroke: case report.

Cardiac hydatid cysts are rarely seen. The presentation of an acute stroke secondary to embolization from a cardiac hydatid cyst is also rare. We report a young boy with left ventricular hydatid cyst who presented with acute ischemic stroke.

Cerebrospinal cuterebriasis in cats and its association with feline ischemic encephalopathy.

Over the past 10 years, 10 cats with primary central nervous system infection by larvae of Cuterebra flies have been documented at Cornell University. Clinical abnormalities noted in all cats were progressive and most commonly consisted of depression (6/10), blindness (6/10), and behavior changes (2/10). Affected cats presented most commonly in July (2/10) and August (7/10); one cat was presented in September. The diverse histopathologic changes are unique to this aberrant migration and consist of a combination of five characteristic features: 1) parasitic track lesion (7/10), 2) superficial laminar cerebrocortical necrosis (10/10), 3) cerebral infarction (8/10), 4) subependymal rarefaction and astrogliosis with or without ependymal cell loss (7/10), and 5) subpial astrogliosis (7/10). Changes 2-5 occurred throughout the parenchyma unassociated with the track lesion or the parasite in the affected tissue. The larvae have been recovered most commonly in the region of the olfactory bulbs and peduncles, optic nerves, and cribriform plate, suggesting entry from the nasal cavity. Many of the changes noted are suggestive of a toxic factor elaborated by the parasite and borne within the cerebrospinal fluid, as well as vascular compromise as a component in those cats with brain infarction. Because of the prevalence of infarction associated with this syndrome and the lack of reported cases of such lesions in regions of the world devoid of the fly, we propose that aberrant cuterebral larval migration in the brain is the cause of feline ischemic encephalopathy.

Frequency of cerebral arteritis in subarachnoid cysticercosis: an angiographic study.

BACKGROUND AND PURPOSE: Subarachnoid cysticercosis is a well-recognized cause of cerebral infarction. However, few patients with this infection develop cerebral infarction, and the reason for this is not known. The aim of this study was to determine the frequency of cerebral arteritis in these patients. METHODS: Using cerebral arteriography, we studied 28 patients with subarachnoid cysticercosis admitted to our hospital from July 1993 to February 1996. All patients underwent MRI to detect the presence of basal arachnoiditis. We analyzed demographic data, time to cysticercosis since the first symptom onset, mode of onset, stroke syndromes, neuroimaging features of cysticercosis and cerebral infarction, and arteriographic findings for each patient. RESULTS: Of the 28 patients (mean age, 37 years), 15 patients had angiographic evidence of cerebral arteritis (53%); 12 of the 15 had a stroke syndrome (P=.02). Eight of the 15 patients (53%) with cerebral arteritis had evidence of cerebral infarction on MRI, whereas only one patient without cerebral arteritis had cerebral infarction (P=.05). The most commonly involved vessels were the middle cerebral artery and the posterior cerebral artery. CONCLUSIONS: The frequency of cerebral arteritis in subarachnoid cysticercosis is higher than previously reported, and middle-size vessel involvement is a common finding, even in those patients without clinical evidence of cerebral ischemia.

Brain swelling and ischaemia in Kenyans with cerebral malaria.

Computed tomography was performed on 14 unconscious Kenyan children recovering from cerebral malaria (seven of whom had another scan 12-120 days later) to elucidate the cause of intracranial hypertension and neurological sequelae. Brain swelling, defined as a loss of cerebrospinal fluid spaces, was documented in six children, while a further two had conspicuously small ventricles only. There was severe intracranial hypertension in the two children with definite brain swelling in whom intracranial pressure was monitored. There was no evidence of acute hydrocephalus or vasogenic oedema. Four children with brain swelling also had widespread low density areas suggestive of ischaemic damage. The patterns of damage were not uniform but were consistent with a critical reduction in cerebral perfusion pressure (which was documented in the two in whom this was monitored), hypoglycaemia, or status epilepticus. All four had serious neurological sequelae. These data suggest that brain injury in cerebral malaria may be due in part to secondary systemic and intracranial factors as well as to the direct effect of intravascular sequestration.