Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions.

Some macrophages expressing NG2 chondroitin sulfate proteoglycan (NG2) and the macrophage marker Iba1 accumulate in the ischemic core of a rat brain subjected to transient middle cerebral artery occlusion (MCAO) for 90 min. These cells are termed BINCs (for brain Iba1(+) /NG2(+) cells) and may play a neuroprotective role. Because BINCs are bone marrow-derived cells, they are able to invade ischemic tissue after the onset of an ischemic insult. In this study, chemokine-based mechanisms underlying the invasion of BINCs or their progenitor cells were investigated. We found that isolated BINCs expressed mRNA encoding CCR2 and CX3CR1 at high levels. Cultured astrocytes expressed mRNA encoding their ligands, MCP-1 and fractalkine. Recombinant MCP-1 and/or fractalkine, as well as astrocytes, induced the migration of BINCs in vitro. mRNA for MCP-1, fractalkine, CCR2, and CX3CR1 was expressed in the ischemic core during the acute phase of the ischemic event. Immunohistochemical studies revealed that vascular endothelial cells and astrocytic endfeet expressed MCP-1 and fractalkine, respectively, in the ischemic core during the acute phase. CCR2(+) /Iba1(+) monocytes attached to the inside of the vascular wall at 1 day postreperfusion (dpr), and there were CCR2(+) /CX3CR1(+) macrophage-like cells in the parenchyma in the ischemic lesion core at 2 dpr, which may be the progenitors for BINCs. These results suggest that CCR2(+) monocytes are first attracted to the ischemic lesion by MCP-1(+) endothelial cells and migrate toward fractalkine(+) astrocytic endfeet through the disrupted blood-brain barrier. Thus, chemokines may play a critical role in the accumulation of neuroprotective BINCs. © 2013 Wiley Periodicals, Inc.

[Two cases of cervical carotid artery stenosis with high risk post-operative hyperperfusion treated with dexmedetomidine after carotid endarterectomy].

Dexmedetomidine is a central alpha2 adrenoceptor agonist recently shown to be a safe and acceptable sedative agent for patients requiring sedation after brain surgery. We report two patients successfully treated by carotid endarterectomy (CEA) with postoperative management under dexmedetomidine anesthesia for transient ischemic attack (TIA) resulting from severe stenosis of the internal carotid artery (ICA). Case 1: A 75-year-old man was admitted to our hospital with aphasia and weakness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on magnetic resonance imaging (MRI)/diffusion-weighted image (DWI), MR angiography (MRA) revealed severe stenosis of the left cervical ICA. (123)I-IMP-single photon emission tomography (SPECT) and transcranial Doppler (TCD) revealed marked reduction of cerebral blood flow in the left cerebral hemisphere. Although CEA induced hyperperfusion, aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged without neurological deficits. Case 2: A 68-year-old man was admitted to our hospital with amaurosis fugax and numbness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on MRI/DWI, MRA disclosed severe stenosis of the left cervical ICA. (123)I-IMP-SPECT revealed extremely low perfusion and disturbance of vascular reactivity in the territory of the left ICA. Although conservative therapy was performed, crescendo TIA was noted. Revascularization using CEA was therefore performed. After surgery, hyperperfusion was observed in the same fashion as in case 1, and again aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged 1 month postoperatively without neurological deficits. Dexmedetomidine is a safe and acceptable sedative drugs preventing hyperperfusion syndrome after CEA.