Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Jan 2010
Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia.
Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [(18)F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. ⋯ Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [(18)F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.
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J. Cereb. Blood Flow Metab. · Jan 2010
The role of bradykinin B(1) and B(2) receptors for secondary brain damage after traumatic brain injury in mice.
Inflammatory mechanisms are known to contribute to the pathophysiology of traumatic brain injury (TBI). Since bradykinin is one of the first mediators activated during inflammation, we investigated the role of bradykinin and its receptors in posttraumatic secondary brain damage. We subjected wild-type (WT), B(1)-, and B(2)-receptor-knockout mice to controlled cortical impact (CCI) and analyzed tissue bradykinin as well as kinin receptor mRNA and protein expression up to 48 h thereafter. ⋯ Immunohistochemistry showed that B(1) and B(2) receptors were expressed in the brain and were significantly upregulated in the traumatic penumbra 1 to 24 h after CCI. B(2)R(-/-) mice had significantly less brain edema (-51% versus WT, 24 h; P<0.001), smaller contusion volumes ( approximately 50% versus WT 24 h and 7 d after CCI; P<0.05), and better functional outcome 7 days after TBI as compared with WT mice (P<0.05). The present results show that bradykinin and its B(2) receptors play a causal role for brain edema formation and cell death after TBI.
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J. Cereb. Blood Flow Metab. · Jan 2010
Arterial spin labeling perfusion MRI at multiple delay times: a correlative study with H(2)(15)O positron emission tomography in patients with symptomatic carotid artery occlusion.
Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) with image acquisition at multiple inversion times is a noninvasive ASL technique able to compensate for spatial heterogeneities in transit times caused by collateral blood flow in patients with severe stenosis of the cerebropetal blood vessels. Our aim was to compare ASL-MRI and H(2)(15)O positron emission tomography (PET), the gold standard for cerebral blood flow (CBF) assessment, in patients with a symptomatic internal carotid artery (ICA) occlusion. Fourteen patients (63+/-14 years) with a symptomatic ICA occlusion underwent both ASL-MRI and H(2)(15)O PET. ⋯ Both PET and ASL-MRI showed a significantly decreased CBF in the gray-matter of the middle cerebral artery in the hemisphere ipsilateral to the ICA occlusion. The average gray-matter CBF measured with ASL-MRI (71.8+/-4.3 mL/min/100 g) was higher (P<0.01) than measured with H(2)(15)O PET (43.1+/-1.0 mL/min/100 g). In conclusion, ASL-MRI at multiple TIs is capable of depicting areas of regions with low CBF in patients with an occlusion of the ICA, although a systematic overestimation of CBF relative to H(2)(15)O PET was noted.
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J. Cereb. Blood Flow Metab. · Jan 2010
Minocycline reduces neuronal death and attenuates microglial response after pediatric asphyxial cardiac arrest.
The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. ⋯ Minocycline attenuated ACA-induced increases in MIP-1alpha and RANTES (P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target.