Takeshi Suma

Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury.

Abstract Objective: Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses. Methods: EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes). Results: Ten minutes after injury, microglial activation with increased OX42 immuno-reactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions. Discussion: These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.

Decrease in doublecortin expression without neuronal cell death in rat retrosplenial cortex after stress exposure.

Exposure to acute stress by forced swim impairs spatial learning and memory in rats. The retrosplenial cortex plays an important role in spatial learning and memory. A cell population that expresses immature neuronal markers, including doublecortin (DCX), plays a key role in plasticity of the adult brain through formation of new neurons. Here, we aimed to determine whether rats exposed to acute stress showed changes in DCX expression in retrosplenial cortex cells. Twelve male Sprague–Dawley rats were used. Six were subjected to acute stress by forced swim (group S), and the remaining six served as controls (group C). Immunohistochemical staining was performed for DCX, neuron-specific nuclear protein, parvalbumin, calbindin, calretinin, and somatostatin. Newly generated cells were immunohistochemically detected by daily administration of 5-bromo-2′-deoxyuridine for 1 week. Fluoro-Jade B staining was performed to detect cell death. Group S showed lower number of DCX-expressing cells than group C (P<0.001). The proportion of DCX-expressing cells showing neuron-specific nuclear protein co-localization (24% in group S; 27% in group C) or parvalbumin co-localization (65% in group S; 61% in group C) remained unchanged after acute stress exposure. Neither 5-bromo-2′-deoxyuridine-positive nor Fluoro-Jade B-positive cells were found in the retrosplenial cortex of groups S and C. DCX-expressing cells in the retrosplenial cortex decreases markedly without cell death after acute stress exposure. Neuronal differentiation of these cells toward gamma aminobutyric acidergic interneurons appears to be unaltered. The decrease in DCX expression may reduce plasticity potential within the retrosplenial cortex and attenuate spatial learning and memory function.

Jugular bulb venous thrombosis caused by mild head injury: a case report

BACKGROUND We present here the first report of a jugular bulb venous thrombosis after mild head injury, which lacked either a skull fracture or abnormal findings on CT scan. CASE DESCRIPTION An 8-year-old boy was hit on the back of the head and experienced headache and vomiting beginning the next morning. A CT scan and cranial x-ray examination failed to reveal any abnormal findings. The patient was treated conservatively; however, his headache and vomiting persisted. At 13 days after the injury, he began to show double vision due to left VIth nerve palsy and bilateral papilloedemas, suggesting an increased ICP. Although repeated CT scan failed to detect abnormal findings in both the supra- and infra-tentorial regions, MRI clearly visualized a thrombus which was situated within the right jugular bulb. Furthermore, MRV demonstrated disruption of venous flow at the jugular bulb. The patient was administered heparin continuously. His symptoms improved and the CSF pressure on lumbar puncture returned to a normal level at 20 days after admission. Magnetic resonance imaging showed resolution of the clot, and MRV appeared to demonstrate partial recanalization simultaneously. The patient was discharged without any neurologic deficits. The clot in the jugular bulb disappeared completely after 4 months, and he could be followed up for 1 year. CONCLUSION This case underscores the fact that MRI may represent the exclusive screening examination in cases of sinus thrombosis when it occurs within the jugular bulb, as CT scan fails to reveal any findings suggestive of venous thrombosis.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS.

Acute Stress Exposure Preceding Global Brain Ischemia Accelerates Decreased Doublecortin Expression in the Rat Retrosplenial Cortex

BACKGROUND Psychological distress is a risk factor of stroke in humans and worsens the behavioral and neurological outcomes. In rats, acute stress exposure preceding ischemic events attenuates learning and memory. The retrosplenial cortex (RS) plays an important role in these functions, and global brain ischemia (GBI) or acute stress exposure can induce a decrease in expression of the immature neuronal marker, doublecortin (DCX), in the RS. However, little is known about the DCX expression in the RS after stress exposure prior to GBI. METHODS Eighteen male Sprague-Dawley rats were used. Acute stress exposure was applied as the forced swim paradigm and GBI was induced by bilateral common carotid arterial occlusion for 10 min. The rats were divided into three groups: GBI model preconditioned by stress (n = 6, Group P), GBI model preconditioned by non-stress (n = 6, Group G), and controls (n = 6, Group C). We performed immunohistochemistry to observe and analyze the DCX-expressing cells and Fluoro-Jade B (FJB) staining to detect cell death in the RS after GBI in each group. RESULTS The total number of DCX-expressing cells was 1,032, 1,219, and 1,904 in Group P, Group G, and Group C, respectively. The mean number of DCX-expressing cells per unit area was significantly lower in Group P and Group G than in Group C (P < 0.001). Moreover, the number was significantly lower in Group P than in Group G (P < 0.05). In each group, no FJB positive cells were observed. CONCLUSION DCX plays an important role in various cytoskeletal changes. Preconditioning by acute stress exposure accelerated the decrease in DCX expression in the RS after GBI.

Monitoring of Hemodynamic Change in Patients with Carotid Artery Stenosis During the Tilt Test Using Wearable Near-Infrared Spectroscopy

Transient ischemic attack (TIA) is a major complication in patients with carotid artery stenosis. Patients with severe stenosis sometimes complain of orthostatic dizziness, such as syncope. The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for evaluating cerebral circulation in patients with carotid artery stenosis during head-up tilt test (HUTT). Fourteen patients with carotid artery stenosis and nine normal control subjects participated. In addition to blood pressure monitoring, hemoglobin (Hb) values (oxy-Hb, deoxy-Hb, and total Hb) were recorded by a wearable NIRS instrument with a high time resolution during HUTT. Oxy-Hb, which decreased initially when the test table was elevated, subsequently increased in normal volunteers and patients with carotid artery stenosis and did not differ significantly between the two groups. However, the oxy-Hb reduction in the carotid artery stenosis group (-0.02 ± 0.03 a.u.) at 30 s after elevation of the table was significantly larger than in the normal group (0.02 ± 0.02 a.u., P < 0.01). Our results indicate that oxy-Hb reduction in patients with carotid artery stenosis may be related to orthostatic dizziness. We concluded that NIRS monitoring is useful for evaluating cerebral autoregulation in patients with severe carotid artery stenosis.

Endovascular Treatment for Ruptured Vertebral Artery Dissecting Aneurysms at the Acute Stage

OBJECTIVE Ruptured vertebral artery dissecting aneurysms (VADA) should be treated promptly because of the high risk of rebleeding. However, it is difficult to treat dissecting aneurysm during the acute stage using microsurgery because of high intracranial pressure or brain edema. Therefore, endovascular treatment of the ruptured VADA may be a better technique. We retrospectively studied the efficacy and outcome of endovascular treatment of ruptured VADA at the acute stage. METHODS Ten patients with ruptured VADA received endovascular treatment at the acute stage. Eight patients who had dissecting aneurysms were treated by internal trapping of the dissected segment. We performed stent-assisted coiling (SAC) for a case of VADA in contralateral hypoplastic VA and a case of bilateral dissections, ruptured VADA of the right VA and VA dissection of the left VA. RESULTS Four patients had good recovery, 3 patients had moderate disability, 2 patients had severe disability, and 1 patient died from initial severe SAH. There was no rebleeding or procedure-related complication. However, one patient who was treated by SAC had ischemic complications post-treatment. CONCLUSION Endovascular treatment of ruptured VADA in the acute stage appears to be safe and effective.

Transplantation of polymer-encapsulated fetal hippocampal cells into ischemic lesions of adult rat hippocampus.

In a previous study we demonstrated that fetal hippocampal cells, when transplanted into ischemic lesions of the adult rat hippocampus, can survive in large numbers in the host brain and show the innervation of the transplants by cholinergic fibers originated from the host brain. The present study was undertaken in an attempt to elucidate the hypothesis that the fiber connections forming synapses between the transplanted fetal neurons and the host brain play an important role in the survival of the transplanted cells. We transplanted the polymer-encapsulated fetal hippocampal cells prepared from E17-18 rat fetuses into the ischemic lesions in the adult rat hippocampus at which the CA1 pyramidal cells selectively died, and examined both histochemically or immunohistochemically for their survival and the expression of the synaptic vesicle protein, synaptophysin, and dendritic cytoskeltal protein, microtubule-associated protein 2 (MAP 2) within them. In addition, the cholinergic fibers originated from the host brain were examined by acetylcholine esterase (AChE) histochemistry. The results demonstrated that the polymer-encapsulated hippocampal cells could survive in the brain; however, the number of surviving cells markedly decreased following the transplantation, whereas no host-derived cholinergic fibers penetrated the polymer membrane of the capsules following the transplantation. In the cluster of surviving cells, only slight synaptophysin expression and no extensive growth of the dendrites were detected. The present results indicate that the direct contact between the host brain tissue and the transplant play an important role in the survival of such allografted neurons.