Atsuo Yamashita

The Temporal Profile of the Reaction of Microglia, Astrocytes, and Macrophages in the Delayed Onset Paraplegia After Transient Spinal Cord Ischemia in Rabbits

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. IMPLICATIONS: Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Tight glycemic control by insulin, started in the preischemic, but not postischemic, period, protects against ischemic spinal cord injury in rabbits

BACKGROUND:It is not well established whether insulin protects against ischemic spinal cord injury. We examined the effects of a single dose of insulin that corrects mild hyperglycemia on the outcome after transient spinal cord ischemia in rabbits. METHODS:We assigned rabbits to four groups (n = 8 in each); untreated control (C) group, preischemic insulin (Pre-I) group, preischemic insulin with glucose (GI) group (glucose concentrations were maintained at levels similar to the C group by the administration of glucose), and postischemic insulin (Post-I) group. Insulin (0.5 IU/kg) was administered 30 min before ischemia in the Pre-I and GI groups, and just after reperfusion in the Post-I group. Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Neurologic and histopathologic evaluations were performed 7 days after ischemia. RESULTS:The mean blood glucose concentration before ischemia in the Pre-I group (118 mg/dL) was significantly lower than in the other three groups (158–180 mg/dL) and those of 30 min after reperfusion in the Pre-I (92 mg/dL) and Post-I (100 mg/dL) groups were significantly lower than in the C (148 mg/dL) and GI (140 mg/dL) groups. The motor function score and number of normal neurons in the anterior lumbar spinal cord in the Pre-I group were significantly greater than in the other three groups. CONCLUSIONS:These results suggest that a relatively small dose of preischemic insulin protects against ischemic spinal cord injury, and that the protective effects result from tight glycemic control before ischemia.

Does high-dose opioid anesthesia exacerbate ischemic spinal cord injury in rabbits?

PurposeIntrathecal morphine given during a post-ischemic period has been reported to have the potential to exacerbate ischemic spinal cord injury. However, it remains unknown whether synthetic opioids administered systemically exacerbate ischemic injury. We sought to compare the damage of the spinal cord after transient spinal cord ischemia in rabbits anesthetized with three different regimens; isoflurane, fentanyl with isoflurane, and remifentanil with isoflurane.MethodsWe assigned rabbits to three groups (n = 9 in each); an isoflurane group (isoflurane 1 minimum alveolar concentration [MAC]), a fentanyl group (isoflurane 0.5 MAC + 100 μg·kg−1 IV fentanyl given over 30 min before aortic occlusion), and a remifentanil group (isoflurane 0.5 MAC + 1 μg·kg−1·min−1 IV remifentanil started 30 min before aortic occlusion and maintained until 1 h after reperfusion). Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Hindlimb motor function (score range: 4, normal to 0, paraplegia) was assessed daily for 7 days, and then the number of normal neurons in the anterior spinal cord was counted.ResultsSevere motor dysfunction (score ≤ 1) was observed in seven, four, and five animals in the isoflurane, fentanyl, and remifentanil groups, respectively. There were no significant intergroup differences in neurological scores. There were no differences in the numbers of normal neurons among the three groups (22 ± 22, 42 ± 30, 33 ± 28, respectively).ConclusionOur results suggest that neither IV fentanyl nor IV remifentanil added to 0.5 MAC isoflurane exacerbated ischemic spinal cord injury in rabbits when compared to 1 MAC isoflurane.

The effects of cyclosporin A and insulin on ischemic spinal cord injury in rabbits.

We examined the effects of cyclosporin A (CsA), a drug that inhibits mitochondrial permeability transition pore, and insulin on ischemic spinal cord damage in rabbits. We assigned rabbits to 5 groups (n = 6 in each); sham barrier-opened group (sham BO), barrier-opened group (BO), barrier-opened-CsA group (BO-CsA), barrier-opened-insulin group (BO-I), and barrier-opened-CsA-insulin group (BO-CsA-I). The blood-spinal cord barrier was opened to facilitate drug penetration by a mild injury to the lumber spinal cord on day 1. CsA (10 mg/kg per day IV) was administered on day 3 to day 5 (total 30 mg/kg). Insulin was administered 30 min before ischemia. In all groups, spinal cord ischemia was produced on day 5 by occluding the abdominal aorta for 13 min. Neurological and histopathological evaluations were performed 4 days after ischemia. In group BO-CsA, blood glucose concentrations were significantly larger compared with the other four groups, and no protection was observed. In contrast, hindlimb motor function in groups BO-I and Bo-CsA-I and histopathology in group BO-CsA-I were significantly better than in groups sham BO, BO, and BO-CsA. The results indicate that insulin protects against ischemic spinal cord injury, whereas the effect of CsA is, at best, minimal.

The effects of an AMPA receptor antagonist on the neurotoxicity of tetracaine intrathecally administered in rabbits.

We have reported that large concentrations of intrathecal local anesthetics increase glutamate concentrations in the cerebrospinal fluid (CSF) and cause neuronal injury in rabbits. In the current study we determined whether an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM872, administered intrathecally, reduces neuronal injury caused by tetracaine. We first examined the effects of intrathecal YM872 10, 30, 100, or 300 μg in rabbits (n = 3 in each). YM872 produced reversible motor and sensory block in a dose-dependent manner. Then, we evaluated modulatory effects of YM872 (300 μg) on tetracaine-induced glutamate release and neuronal injury. Pretreatment of YM872 did not attenuate 1% or 2% tetracaine-induced increases in cerebrospinal fluid glutamate concentrations (n = 3 in each). For evaluation of neuronal injury, rabbits were assigned to 4 groups (n = 6 in each) and intrathecally received 1% tetracaine and saline (1%T), 1% tetracaine and YM872 (1%TY), 2% tetracaine and saline (2%T), or 2% tetracaine and YM872 (2%TY). The volume of saline, YM872, and tetracaine was 0.3 mL. Saline or YM872 was administered 30 min before tetracaine administration. Neurological and histopathological assessments were performed 1 wk after the administration. Two and 1 animals respectively, showed motor and sensory dysfunction in 1%T, whereas 5 animals showed both motor and sensory dysfunction in 2%T. YM872 improved 2% tetracaine-induced motor dysfunction and neuronal damage (chromatolytic neurons, identified by round-shaped cytoplasm with loss of Nissl substance from the central part of the cell and eccentric nuclei). In 2%TY, 3 animals showed normal motor function and 3 showed mild dysfunction (ability to hop, but not normally), whereas 4 animals showed moderate dysfunction (inability to hop) in 2%T (P = 0.042). Only 2 animals showed one chromatolytic neuron in 2%TY, whereas 5 animals showed 4–16 chromatolytic neurons in 2%T (P = 0.020). These results suggest that AMPA receptor activation is involved, at least in part, in the tetracaine-induced neurotoxicity in the spinal cord.

Present Clinical Status of Postoperative Cognitive Dysfunction in Cardiovascular Surgery

Postoperative cognitive dysfunction (POCD) is one of the serious cerebral complications that occur after cardiac and major vascular surgery, leading to low quality of life and poor prognosis of the patients. POCD has been comprehensively investigated in coronary artery bypass grafting surgery with cardiopulmonary bypass (CPB) to elucidate its risk factors and to seek a better management that can reduce the development of POCD. However, in patients with coronary artery disease, the long-term (>6 months) incidence rate of cognitive dysfunction did not differ significantly in four treatment groups (coronary artery bypass grafting surgery with, or without CPB, percutaneous coronary intervention, and drug therapy plus follow-up observation). These findings suggest that surgery and CPB affect cognitive impairment for only about 6 months after surgery. On the other hand, there is no well-designed study for POCD with sufficient number of patients in valvular and major vascular surgery. Future challenges need the elucidation of long-term incidence rate of POCD in these surgeries and should include the patients with less invasive procedure such as transcatheter aortic valve implantation and thoracic endovascular aortic repair surgery.

Correction to: Cerebrovascular CO 2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure

In the original publication of the article, the first sentence was published incorrectly under the section “Patients and preoperative assessment”. The correct sentence should read as, “The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)”.

1-Year Follow-Up of Contained Aortic Root Rupture After Transcatheter Aortic Valve Replacement

The authors performed a transfemoral aortic valve replacement (TF-TAVR) in an 89-year-old woman with severe aortic stenosis. The pre-operative transthoracic echocardiography (TTE) revealed severe aortic stenosis (aortic valve area 0.6 cm2) with huge calcifications at each leaflet. At multislice

Coronary obstruction occurring 72 h after transcatheter aortic valve replacement with a self-expandable valve

Article history: Received 6 July 2016 Accepted 5 August 2016 Available online 07 August 2016 tive valve close to the LCA ostium. After dilation using a 20-mmballoon, paravalvular leakage was reduced from moderate to mild without any significant findings of myocardial ischemia. Her hemodynamic status was stable and final aortography showed no coronary flow impairment (Fig. 1). Three days after TAVR, she complained of sudden strong dyspnea.

Role of Transcranial Doppler Ultrasonography in Neuroanesthesia

Transcranial Doppler ultrasonography (TCD) allows easy bedside monitoring of cerebral circulation and can be used repeatedly and continuously at low cost. A high level of skill is required to obtain a sonogram of an individual blood vessel through the transtemporal bone window with this technique. However, the use of transcranial color duplex imaging and the power motion mode has further facilitated the measurement of blood flow velocity in the brain by this method. Cerebral autoregulation and cerebrovascular CO2 reactivity can be determined by TCD and are useful prognostic indicators in patients with cerebral infarction, subarachnoid hemorrhage, or head trauma. Transcranial Doppler ultrasonography is also suitable in evaluating cerebrovascular stenosis, vasospasm following subarachnoid hemorrhage, vascular patency following cerebral infarction and cerebral circulation in patients with intracranial hypertension. Furthermore, microemboli that have disseminated to the brain during carotid endarterectomy or cardiovascular surgery can be detected by TCD as microembolic signals. New techniques to differentiate between gaseous and solid microemboli are currently under development. We anticipate that the utility of TCD as a useful bedside monitoring tool for evaluating cerebral circulation will become increasingly recognized.