Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study.

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

Evolution of early perihemorrhagic changes--ischemia vs. edema: an MRI study in rats.

OBJECTIVES: Cerebral ischemia has been proposed as a contributing mechanism to secondary neuronal injury after intracranial hemorrhage (ICH). The search for surrogate parameters that allow treatment stratification for spontaneous ICH continues. We aimed to examine perihemorrhagic ischemic changes with an animal experimental MRI study. METHODS: A high field MRI compatible setup for male Wistar rats was established using a double injection model. ICH was stereotactically placed into the right basal ganglia of 29 Wistar rats. Coronal T2-WI, T2*-WI and DWI were generated with a 2.35 T animal MRI scanner 15 min, 60 min and 210 min after ICH. Clot signal characteristics, clot volumes and normalized ADC values were analyzed in four hematoma regions (core, periphery, outer rim, healthy ipsilateral tissue) in all sequences. RESULTS: T2*-WI and DWI reliably demonstrated ICH in 100% with only small deviation from the applied volume (-20% to +26%) whereas T2-WI failed to conspicuously show ICH. There were no perihemorrhagic ADC decreases consistent with ischemic cytotoxic edema but a mild vasogenic edema surrounding the ICH could be observed. CONCLUSION: T2*-WI and DWI are accurate for the diagnosis of hyperacute ICH. According to serial and crossectional ADC analysis, there is no hint towards the existence of a perihemorrhagic ischemic area that might be saved by early intervention. Future studies should focus on perfusion and metabolic/neurotoxic studies of this particular area and neurotoxic properties of the surrounding edema.

Experimental herpes simplex virus encephalitis: a long-term study of interleukin-6 expression in mouse brain tissue.

This study aimed to investigate the expression of interleukin-6 (IL-6) in acute and chronic herpes simplex virus encephalitis. In the brain of 15 SJL mice infected with herpes simplex virus type 1, strain F, and 14 control animals we performed a sequential quantitative analysis of expression of IL-6 mRNA with reverse transcription real-time polymerase chain reaction. The viral burden peaked in the acute disease, and then returned to a low baseline value. At day 7 following infection, IL-6 expression was significantly (2.05-fold) increased as compared with the baseline expression in uninfected animals. Twenty-one days after infection the mRNA expression still was significantly (1.78-fold) upregulated. No significant differences of IL-6 mRNA expression between infected and control mice were found after 2 and 6 months. We observed a 2.5-fold increase of IL-6 mRNA expression in control mice with increasing age of animals. We have additionally studied the clinical evolution of HSVE in IL-6 deficient mice. In experimental herpes simplex virus encephalitis IL-6, as a potent mediator of neuronal injury, is upregulated in the acute but not in the chronic disease. IL-6 deficient mice presented early and severe clinical signs of HSVE as compared to the wild-type C57/bl6 mice.

[The value of platelet inhibitors in the secondary prophylaxis of stroke -- a review]. / Stellenwert von Thrombozyten-Aggregationshemmern in der Sekundärprävention des ischämischen Schlaganfalls.

INTRODUCTION: The goal of secondary prophylaxis following cerebral ischemia is a long lasting inhibition of thrombogenesis to prevent recurrent stroke or other vascular events. Platelet inhibitors (PI) according to meta-analyses lead to a relative risk reduction (RRR) of 22 % for vascular events after stroke. The aim of this article is a summary and critical review of all relevant studies and meta-analyses for secondary prevention of stroke and to give a differentiated therapeutic recommendation. METHODS: We performed a careful and extensive review of the present literature for PI in the secondary prevention of stroke. Next to the classic meta-analyses such as the Antiplatelet Trialists' analysis, the relevant single trials (e. g. CATS, TASS, ESPS 2, CURE, CAPRIE) as well as meta-analyses and post hoc analyses of these studies are summarized and interpreted. Therapeutic recommendations are in consistence with the recommendations and guidelines of national (DGN), European (EUSI) and international (AHA/ASA) Groups/Associations. Also, the present literature was searched for new information with regard to side effects and pharmacological interactions and introduced into the review. CONCLUSIONS: ASA reduces the RR after TIA/stroke by approximately 13 % and has the same efficacy with less side effects in lower dosages (50 - 325 mg/Tag). Ticlopidine is a reserve drug due to its unfavorable side effect profile (neutropenia, TTP). Clopidogrel is better than ASA (RRR 8.7 %) for vascular patients in preventing another vascular event (stroke, MI, vascular death). This effect is pronounced in patients at high risk for atherothrombotic events such as previous MI, cardiac surgery, or diabetes. Dipyridamole+ASA is better than ASA in patients with TIA/stroke (in indirect comparison also than Clopidogrel) for the secondary prevention of recurrent stroke (RRR 23 %), but not for the prevention of other vascular events. Therefore, Clopidogrel should be primarily given to patients with a high vascular risk (one or more cardiovascular risk factors) or to patients with ASA intolerance. Dipyridamole/ASA should be primarily given to TIA/stroke patients with a lower cardiovascular comorbidity. Studies for the combination of Clopidogrel/ASA (MATCH, CHARISMA) and for the comparison of both combinations (PRoFESS) are underway. At present, the combination of clopidogrel and ASA for cerebrovascular prevention should only be given within controlled studies or as an individual treatment with an accordingly acquired informed consent.

Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities.

Despite early antiviral treatment, herpes simples virus encephalitis (HSVE) still remains a life-threatening sporadic disease with high mortality and morbidity. In patients and in experimental disease, chronic progressive magnetic resonance imaging (MRI) abnormalities have been found even after antiviral therapy. Secondary autoimmune-mediated and not directly virus-mediated mechanisms might play a key role for the outcome of disease. This study aimed to evaluate a possible beneficial effect of a therapy of acyclovir and corticosteroids versus acyclovir only. In a mouse model of HSVE (intranasal inoculation with 10(5) pfu [plaque-forming units] of HSV-1 strain F), a long-term MRI study was realized. Cranial MRI was performed serially at days 2, 7, 14, 21, 60, and 180 in different therapy groups: 1, saline; 2, acyclovir; 3, acyclovir, subsequently methylprednisolone; 4, sham-infected with saline. Brain viral load peaked at day 7 to decline thereafter to a low baseline value. Viral load in group 1 was significantly higher than in animals with antiviral therapy. In group 4, no viral DNA was detectable. Viral load did not differ significantly between acyclovir and acyclovir/corticosteroid-treated groups, suggesting that the use of corticosteroids in addition to acyclovir does not increase viral burden. MRI findings in untreated and acyclovir-treated animals revealed chronic progressive changes. In contrast, there was a significant reduction of the severity of long-term MRI abnormalities in acyclovir/corticosteroid-treated animals. With respect to abnormal MRI findings, this study demonstrates a clear beneficial effect of an acyclovir and corticosteroid therapy without influencing brain viral load.