The contribution of 3D-CISS and contrast-enhanced MR cisternography in detecting cerebrospinal fluid leak in patients with rhinorrhoea.

The aim of this prospective study was to evaluate the value of unenhanced (three-dimensional constructive interference in steady state (3D-CISS)) and contrast-enhanced MR cisternography (CE-MRC) in detecting the localisation of cerebrospinal fluid (CSF) leak in patients with rhinorrhoea. 17 patients with active or suspected CSF rhinorrhoea were included in the study. 3D-CISS sequences in coronal and sagittal planes and fat-suppressed T1-weighted spin-echo sequences in three planes before and after intrathecal contrast media administration were obtained. Images were obtained of the cribriform plate and sphenoid sinus. In addition, high-resolution CT (HRCT) was performed in order to evaluate the bony elements. The leak was present in 9/17 patients with 3D-CISS and 10/17 patients with CE-MRC. The leak from the cribriform plate to the nasal cavity in six patients and from the sphenoid sinus in four patients was nicely shown by CE-MRC. Eight of those patients were surgically treated, but spontaneous regression of the symptoms in two precluded any intervention. The leak localisations shown with CE-MRC were fully compatible with surgical results. The sensitivities of HRCT, 3D-CISS and CE-MRC for showing CSF leakage were 88%, 76% and 100%, respectively. In conclusion, 3D-CISS is a non-invasive and reliable technique, and should be the first-choice method to localise CSF leak. CE-MRC is helpful in conditions when there is no leak or in complicated cases with a positive beta2-transferrin measurement.

Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats.

The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83; p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/-0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group 3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/-0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.

Minimally invasive awake craniotomy using Steiner-Lindquist stereotactic laser guidance.

INTRODUCTION: Awake craniotomy permits the continuous assessment of intraoperative neurological functions. In addition, stereotactic laser guidance aids in performing minimally invasive procedures related to the radical resection of lesions located in eloquent and non-eloquent brain regions. METHODS: Between May 2000 and October 2006, 117 consecutive patients with various intracranial tumoral lesions underwent 141 resection procedures. The eloquent areas were determined with the aid of anatomic landmarks and/or functional MRI (fMRI) examinations. The resection of the lesions was performed under continuous neurological examination. In all cases, postoperative MRI was performed within 24-72 h. RESULTS: Seventy-seven males and 40 females were included in this study. The mean age of the patients was 52.0+/-12.6 years. Most of the lesions were located within the parietal lobe. Of the lesions, 33 (23.4%) were located within the cortex, whereas 108 (76.5%) were subcortical. The most common pathologies were metastasis (70 cases) and glioblastome multiforme (27 cases). In 20 (14.2%) of the patients, fMRI was performed preoperatively. Of 21 patients with multiple lesions, 18 underwent 2 craniotomies and 3 underwent 3 craniotomies. The mean operation time was 72+/-0.3 min, and the mean hospital stay was 3.26+/-1.82 d. The average lesion size was 11.92+/-15.26 cm(3). In 7 cases (4.9%), the surgery caused either new neurological deficits or a worsening of the existing deficits; these deficits were permanent in 2 (1.4%) cases. One patient (0.7%) died due to the development of postoperative intracerebral hemorrhage. CONCLUSIONS: Awake craniotomy with the aid of stereotactic laser guidance is a safe procedure that assists in performing minimally invasive resection of lesions in eloquent and non-eloquent brain regions. Although direct intraoperative stimulation was not performed, detection of the functioning areas of the brain with fMRI decreased additional postoperative neurological deficits. Overall, this method decreased the operation time and hospital stay.

Risk factors and complications of intracranial pressure monitoring with a fiberoptic device.

We prospectively investigated the complications associated with intraparenchymal intracranial pressure (ICP) monitoring using the Camino intracranial pressure device. A fiberoptic ICP monitoring transducer was implanted in 631 patients. About half of the patients (n=303) also received an external ventricular drainage set (EVDS). The durations (mean+/-SD) of ICP monitoring in patients without and with an EVDS were 6.5+/-4.4 and 7.3+/-5.1 days, respectively. Infection occurred in 6 patients with only an ICP transducer (6/328, 1.8%) and 24 patients with an EVDS also (24/303, 7.9%). The duration of monitoring had no effect on infection, whereas the use of an EVDS for more than 9 days increased infection risk by 5.11 times. Other complications included transducer disconnection (2.37%), epidural hematoma (0.47%), contusion (0.47%), defective probe (0.31%), broken transducer (0.31%), dislocation of the fixation screw (0.15%), and intraparenchymal hematoma (0.15%). In conclusion, intraparenchymal ICP monitoring systems can be safely used in patients who either have, or are at risk of developing, increased ICP.

Rupture of a small middle cerebral artery aneurysm into middle fossa arachnoid cyst presenting as a chronic subdural haematoma.

The rupture of an aneurysm into an arachnoid cyst and subdural space is unusual. A 25-year-old man was admitted 2 weeks after having undergone a burr hole drainage for a chronic subdural haematoma elsewhere. An angiogram revealed a small aneurysm at the bifurcation of the middle cerebral artery. The aneurysm was clipped and the cyst communicated with the basal cisterns. To the best of our knowledge, this is the first report of an association of an aneurysm of the middle cerebral artery with an arachnoid cyst presenting as a chronic subdural haematoma.

Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results.

The objective of this study was to investigate the diagnostic value of serum tau protein in determining the severity of traumatic brain injury in patients with mild traumatic brain injury (mTBI) and high-risk patients. Adult patients who presented to our emergency department (ED) with mTBI over 1 year were prospectively enrolled. Patients underwent cranial computed tomography (CT) and were subdivided into high- and low-risk groups, according to the probability of resultant intracranial injury. Serum tau levels of 60 patients and 20 healthy volunteers, who served as a control group, were measured. The mean age of the 60 patients (45 males, 15 females) was 32.5 years (range, 15-66 y). Mean Glasgow Coma Scale (GCS) score was 14+/-0.6. CT scans demonstrated intracranial injury in 11 patients (18.3%) and depressed fracture in 4 patients (6.7%). Serum tau levels of patients (188+/-210 pg/mL), compared with those of controls (86+/-48 pg/mL), were relatively higher; however, differences were not statistically significant (P=.445). Also, serum tau levels of high-risk patients (307+/-246 pg/mL) were significantly higher than those of low-risk patients (77+/-61 pg/mL) (P=.001). A total of 48 patients (80%) were accessible for follow-up after 6 months. Postconcussive syndrome was observed in 8 patients, 5 of whom had serum tau protein levels that were higher than those of the other 3 patients. However, no statistically significant difference was observed (P>.05). Investigators of the present study noted that serum tau levels in patients with mTBI were increased. Therefore, it is believed that this biomarker may prove helpful in identifying high-risk patients with mTBI. However, additional studies are needed to establish the diagnostic value of serum tau in detecting traumatic brain injury in patients with mTBI.

Traumatic epidural haematomas of nonarterial origin: analysis of 30 consecutive cases.

BACKGROUND: The purpose was to analyse the clinical and radiological findings, and management approaches used in 30 consecutive cases of traumatic epidural haematoma of nonarterial origin treated at one centre. METHOD: Medical records for 30 patients surgically treated for epidural haematoma of nonarterial origin between 1997 and 2003 were reviewed. Epidural haematoma of nonarterial origin was diagnosed based on computed tomography (CT) and the bleeding source was confirmed intra-operatively. Admission status, outcome, fracture location, haematoma location/size/volume, and additional intracranial pathology were among the data noted. Two groups were formed for analysis: venous sinus bleeding (group 1) and other venous sources (group 2). FINDINGS: The 30 cases accounted for 25% of the total number of traumatic epidural haematomas (n = 120) treated during the same period. The epidural haematomas of nonarterial origin locations were transverse sigmoid sinus (n = 11; 36.7%), superior sagittal sinus (n = 6; 20%), venous lakes (n = 5; 16.6%), diploë (n = 5; 0.16%), arachnoid granulations (n = 2; 6.7%), petrosal sinus (n = 1; 3.3%). There were 12 postoperative complications in 9 patients: recurrence (n = 4; 13.3% of the 30 total), pneumonia (n = 4; 13.3%), meningitis (n = 2; 6.7%), hydrocephalus (n = 1; 3.3%) and subdural effusion (n = 1; 3.3%). All recurrence cases were re-explored. Six (20%) patients died. Glasgow Outcome Scale (GOS) scores (mean follow-up 13.3 +/- 7.8 months) revealed 22 (73.3%) patients with favourable results (GOS 4-5) and 8 (26.7%) had poor results (GOS 1-3). CONCLUSIONS: Cases of epidural haematoma of nonarterial origin differ from the more common arterial-origin epidural haematomas with respect to lesion location, surgical planning, postoperative complications, and outcome. Epidural haematoma of nonarterial origin should be suspected if preoperative CT shows a haematoma overlying a dural venous sinus or in the posterior fossa and convexity. The sinus-origin group had a high frequency of fractures which crossed the sinuses, and this might be diagnostically and surgically useful in such cases.

Primary-isolated optic nerve sarcoidosis.

Sarcoidosis is a systemic, idiopathic granulomatous disorder with occasionally surprising clinical presentations. A primary involvement of the optic nerve is particularly important due to visual prognosis. We report here a patient with occult sarcoidosis who presented to us with progressive visual loss as the first and primary manifestation of the disease. The patient underwent surgery for histopathological diagnosis and decompression of the optic nerve. This case demonstrated that sarcoidosis should be considered in the differential diagnosis of any lesion involving the optic nerve.

Experimental subarachnoid haemorrhage models in rats.

There is no comprehensive and reliable model available in small animals that are suitable for the study of subarachnoid haemorrhage (SAH). In the study we reviewed the advantages and disadvantages of available SAH models in rats and presented our model. Experimental SAH was induced in a group of 350-450 g Sprague-Dawley rats. A 2 mm-diameter burr hole was drilled and, working under a microscope, haemorrhage was produced by transclival puncture of the basilar artery with a 20 microns thick piece of glass. The rats were assigned to either the experimental group (n: 7) or the control group (n: 7). Local cerebral blood flow (LCBF), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured for 60 min after SAH, after which the rats were decapitated. Microscopic examinations were done on three different segments of the basilar artery. There was a significant and sharp drop in LCBF just after SAH was induced (56.17 +/- 12.80 mlLD/min/100 g and 13.57 +/- 5.85 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001), the flow slowly increased by the end of the experiment but never recovered to pre-SAH values (43.63 +/- 7.6 mlLD/min/100 g, p < 0.05). ICP (baseline 7.33 +/- 0.8 mmHg) increased acutely to 70.6 +/- 9.2 mmHg, and also returned to normal levels by 60 min after SAH. CPP (baseline 75.1 +/- 4.9 mmHg) dropped accordingly (to 21.0 +/- 6.3 mmHg) and then increased, reaching 70.1 +/- 4.9 mmHg at 60 min after SAH. Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer. We present an inexpensive and reliable model of SAH in the rat that allows single and multiple haemorrhages and to study the early and late course of pathological changes.

Propofol versus isoflurane anesthesia under hypothermic conditions: effects on intracranial pressure and local cerebral blood flow after diffuse traumatic brain injury in the rat.

BACKGROUND: The aim of this study was to compare the cerebral protective effects of two known protective anesthetics, isoflurane and propofol, when these were used in combination with moderate hypothermia (33-34 degrees C) after diffuse traumatic brain injury (TBI) in the rat. We assessed cerebral protection by measuring local cerebral blood flow (LCBF), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and intracranial pressure (ICP). METHODS: Sixteen female Wistar rats weighing 275 to 350 g were anesthetized and subjected to an accelerated-impact weight-drop model of diffuse TBI. Hypothermia (33-34 degrees C) was induced 45 minutes after TBI (baseline), and was maintained for 180 minutes. The isoflurane group (n = 8) received 70% N(2)O in O(2), and isoflurane at 0.9 +/- 0.04%. The propofol group (n = 8) received 70% N(2)O in O(2) and a propofol infusion (12 mg/kg/hr). LCBF was measured by laser Doppler flowmeter. MABP, ICP, and brain and rectal temperatures were measured every 15 minutes from baseline through 180 minutes. Blood gas and hematocrit testing was also done at baseline and every 60 minutes thereafter to assess the animals' physiological state. RESULTS: In the isoflurane group, MABP and CPP decreased significantly from baseline to 180 minutes (p < 0.05 and p < 0.01, respectively), and MABP was significantly lower than the pressure in the propofol group from 45 minutes through 180 minutes (p < 0.05, p < 0.01). ICP and LCBF remained unchanged in this group. In the propofol group, from baseline to 180 minutes, CPP increased to maximum 120 +/- 8 mmHg at 75 minutes from 98 +/- 5 mmHg (p < 0.05) and ICP fell from 18 +/- 2 mmHg to 7 +/- 1 mmHg (p < 0.01); and the latter was significantly lower than ICP in the isoflurane group (p < 0.05, p < 0.01, p < 0.001). LCBF in this group was significantly higher than LCBF in the isoflurane group in the last 30 minutes of the experiment (p < 0.05). The propofol group showed no change in MABP over the course of the experiment. CONCLUSION: In the clinical setting, propofol anesthesia may be better for use in combination with hypothermia in cases of traumatic brain injury, as it reduces ICP and increases CPP under these conditions.

The effect of hair on infection after cranial surgery.

OBJECTIVE: Reports of large series of patients who had undergone successful cranial neurosurgery without hair removal led part of our team to abandon the practice of shaving patients' heads pre-operatively. The aim of this study was to assess whether this change in routine, which was implemented in 1992, has affected the rate of postoperative infection in our cranial surgery patients. METHODS: A group of patients whose heads were shaved pre-operatively was compared to a group whose hair was not shaved prior to cranial surgery. The latter patients had their hair washed with shampoo and 4% chlorhexidine within 24 hours of their operation. In the operating room, the surgical site was scrubbed for 8-10 minutes with 4% chlorhexidine diluted with water, and then cleansed with 10% povidone-iodine solution. Prophylactic antibiotics were administered for 3 days. RESULTS: We performed 1,038 cranial procedures without hair removal. The procedures included craniotomy for tumour, trauma, aneurysm, other vascular lesions and intracerebral haemorrhage (n = 847), stereotactic biopsy (n = 90), stereotactic craniotomy (n = 34), ventriculoperitoneal shunt placement (n = 27), surgical treatment of infection with aspiration of brain abscess or resection of infected tissue (n = 14), microvascular decompression for trigeminal neuralgia or hemifacial spasm (n = 11), and other miscellaneous procedures (n = 15). We observed 13 postoperative wound infections (1.25%), including 9 deep (0.87%) and 4 superficial infections (0.39%). There was no significant difference between the rate of infection in patients whose heads were shaven (12/980) and the rate in those whose hair was spared (13/1038) (p > 0.05). In addition. there were no other problems related to the surgical preparation technique in the latter group. CONCLUSION: Cranial surgery without hair removal is safe and does not increase the risk of surgical wound infection. Patients naturally prefer to keep their full head of hair. We believe that preoperative hair removal is not necessary in preparation for any type of cranial neurosurgery.

Minimally invasive craniotomy using the Steiner-Lindquist stereotaxic guide.

Thirty-three obscure intracranial lesions were located using the Steiner-Lindquist microsurgical stereotaxic guide and then surgically resected. Seventeen of the lesions were located in the parietal region, six in the frontal region, three in the parietooccipital region, three in the temporoparietal region, one in the thalamic region, one in the centrum semiovale, one in the brainstem, and one in the third ventricle. Twenty-three lesions were in subcortical or cortical locations. In 28 cases, the lesion was totally removed, while in 5 the lesion was subtotally resected. Pathological examinations confirmed glial tumor in eight patients, metastasis in seven, meningioma in two, cavernous angioma in eight, arteriovenous malformation (AVM) in four, hematoma in two, dysembryoblastic neuroepithelial tumor in one, and septum pellucidum cyst in one. Two patients developed transient complications postsurgery. Mean lesion size was 23 +/- 0.97 mm. The hospitalization period ranged from 1 to 6 days (mean 3.4 +/- 1.3 days). Surgeries were performed under general anesthesia, or under local anesthesia with the patient awake. The Steiner-Lindquist microsurgical stereotaxic guide is useful for pinpointing small lesions, especially those in the subcortical and deep areas. Knowing the precise location of the lesion facilitates removal through a small craniotomy incision. This minimally invasive procedure reduces the number of postoperative neurological complications, and also cuts costs by shortening the hospital stay.

The effects of sevoflurane and isoflurane on intracranial pressure and cerebral perfusion pressure after diffuse brain injury in rats.

Twenty-four adult male Wistar rats, weighing 220 to 290 g, were anesthetized with 30 mg/kg intraperitoneal sodium thiopental, then underwent a tracheostomy. After diffuse impact-acceleration brain injury (BI) was induced, each rat was paralyzed and mechanically ventilated with 30% O2 in nitrous oxide (N2O). The rats were assigned randomly to two groups, each of which received one of the two volatile anesthetic agents, sevoflurane or isoflurane. The anesthetics were administered at 0.5, 0.75, 1.0, and 1.25 minimal alveolar concentration (MAC) for 30 minutes each, respectively, and anesthesia was maintained at 0.75 MAC during the last hour of the study period. Intracranial pressure (ICP), mean arterial pressure (MAP), rectal and intrahemispheric temperatures, and end-tidal volatile anesthetic concentrations were monitored continuously throughout the 3 hours, with measurements recorded every 15 minutes. At baseline, there were no significant differences between the two groups regarding the monitored physiologic values. In the sevoflurane group, MAP fell significantly after 45 minutes, and a similar change was observed in the isoflurane group after 30 minutes (P < .05, P < .01, and P < .001, respectively). Intracranial pressure increased significantly at 45 minutes in the sevoflurane group (P < .01) and remained elevated from 60 minutes until the end of the study period (P < .01, P < .001). Although ICP increased in the isoflurane group, the change was not significant. Cerebral perfusion pressure (CPP) decreased in parallel with MAP, with the reduction in the sevoflurane group being more pronounced than that in the isoflurane group. The results demonstrated that, under the conditions of diffuse BI, animals that were anesthetized with sevoflurane had higher ICP and lower CPP levels than those anesthetized with isoflurane.

Acute and delayed vasoconstriction after subarachnoid hemorrhage: local cerebral blood flow, histopathology, and morphology in the rat basilar artery.

The decreased local cerebral blood flow (LCBF) and cerebral ischemia that occur after subarachnoid hemorrhage (SAH) may be caused by acute and/or delayed vasospasm. In 36 Sprague-Dawley (350-450 g) rats SAH was induced by transclival puncture of the basilar artery. Mean arterial blood pressure (MABP), LCBF, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured in all rats for 30 min before and 60 min after SAH was induced. One set of control (n : 7) and experimental animals (n : 7) was sacrificed after the 60 min of initial post-hemorrhage measurements were recorded. Four days after SAH induction, LCBF and MABP were measured again for 60 min in subgroups of surviving experimental rats (n : 7) and control rats (n : 7). Histopathologic and morphologic examinations of the basilar artery were performed in each subgroup. There was a sharp drop in LCBF just after SAH was induced (55.50 +/- 11.46 mlLD/min/100 g and 16.1 +/- 3.6 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001). The flow then gradually increased but had not returned to pre-SAH values by 60 min (p < 0.05). At 4 days after SAH induction, although LCBF was lower than that observed in the control group and pre-SAH values, it was not significantly different from either of these flow rates (p > 0.05). ICP (baseline 7.05 +/- 0.4 mmHg) increased acutely to 75.2 +/- 7.1 mmHg, but returned to normal levels by 60 min after SAH. CPP (baseline 84.5 +/- 6.3 mmHg) dropped accordingly (to 18.6 +/- 3.1 mmHg), and then increased, reaching 72.2 +/- 4.9 mmHg at 60 min after SAH (p > 0.05). Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer in the early stage. LCBF in nonsurviver rats (n : 8) was lower than that in the animals that survived (p < 0.01). At 4 days post-hemorrhage, the rats' basilar arteries showed marked vasculopathy. The findings showed that acute SAH alters LCBF, ICP, and CPP, and that decreased LCBF affects mortality rate. Subsequent vasculopathy occurs in delayed fashion, and this was observed at 4 days after the hemorrhage event.

Effects of interrupted and uninterrupted occlusion of the basilar artery on cerebral blood flow, and on neurological and histological outcome in rats with subarachnoid hemorrhage.

Most neurosurgeons consider temporary vessel occlusion for aneurysmal clipping an effective technique that facilitates dissection between the aneurysm and the parent vessel. It is generally believed that repeated short periods of cerebral ischemia are safer for the brain than a single long episode. The aim of this study was to identify whether interrupted and uninterrupted vessel occlusion differs with regard to changes in brain tissue and cerebral hemodynamics after subarachnoid hemorrhage (SAH). Fifty Spraque Dawley rats (300-350 g) were placed under general anaesthesia and ventilated. The basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values was measured, and then the basilar artery was punctured, causing subarachnoid hemorrhage (SAH). Group I (n = 24) was subjected to 60 min of interrupted basilar artery occlusion, defined as 5 min of reperfusion after every 10 min of occlusion, group II (n = 26) 60 min of uninterrupted artery occlusion. Three days after completion of the experiment, each rat was neurologically evaluated and decapitated. Coronal brain slices were obtained and stained to assess infarct volume. Immediately after SAH, LCBF fell by 58% in group I, and by 52% in group II. In group I, each ischemic insult brought a similar reduction in LCBF, and after each release of the occlusion there was a rapid rise in flow. In group II, the LCBF values dropped initially and remained at low levels until the end of the study. The 2,3,5 triphenyltetrazolium chloride stained sections showed similar volumes of brainstem infarction in both groups (38.3 +/- 9.2 mm3 vs. 34.3 +/- 8.7 mm3, respectively; p > 0.05). The results suggest that there is no neuroprotective advantage to either interrupted or uninterrupted temporary blockage of blood flow during neurovascular procedures after SAH in the basilar artery region.

Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats.

Although accumulating evidence suggests that increased extracellular glutamate concentrations may play an important role in hypoxic-ischemic brain injury, dopamine and other catecholamines also seem to be involved. The N-methyl-D-aspartate receptor antagonist MK 801 and moderate hypothermia (32-34 degrees C) are each known to be neuroprotective, but their combined effect on the release and metabolism of neurotransmitters is unknown. Seven-day-old pups (n: 150) underwent right common carotid artery ligation to induce hemispheric ischemia, and were later subjected to 120 minutes of hypoxia with 8% O2 and 92% N2O. Half the rats (Group I, n: 74) were subjected to normothermic conditions throughout the hypoxic period. Moderate hypothermia (30-32 degrees C) was induced in the other pups (Group II, n: 76) immediately after artery occlusion, and was maintained throughout the hypoxic period. Prior to inducing hypoxia, half of the rats in each group (Groups IA and IIA) received vehicle solution (0.9% NaCI) and the other rats (Groups IB and IIB) received MK 801 (0.5 mg/kg) subcutaneously at 45 and 120 minutes after occlusion. Intracerebral temperature was recorded every 15 minutes after occlusion. Infarct area (n: 40) was calculated after staining with 2% 2,3,5 triphenyltetrazolium chloride. Neuronal damage (n: 42) was assessed by quantifying CA1-CA3 neuronal loss at five hippocampal levels. The amount of damage to the monoamine system of the corpus striatum was determined based on the dopamine and 3,4 dihydroxyphenylacetic acid levels in the corpus striatum in both hemispheres (n: 46), as measured by high-pressure liquid chromatography and compared with normal control pups' values (n: 10). The normothermia/saline-treated pups had significantly larger infarct areas than the MK 801 only, hypothermia only, or MK 801/hypothermia combination groups. Neuropathological examination and striatal tissue monoamine data also confirmed marked neuronal damage in this group. Although MK 801 treatment alone resulted in significantly smaller infarct area and less tissue damage than was observed in the normothermia/saline-treated group, the moderate hypothermia and the MK 801/hypothermia combination treatment groups both exhibited better neuronal protection, especially in the corpus striatum. The rats that received combined treatment also had a significantly lower mortality rate.

Ischemic brain injury caused by interrupted versus uninterrupted occlusion in hypotensive rats with subarachnoid hemorrhage: neuroprotective effects of citicoline.

This study investigated the neuroprotection provided by cytidine 5'-diphosphocholine (citicoline) during interrupted and uninterrupted occlusion of the basilar artery after subarachnoid hemorrhage (SAH) in 121 hypotensive rats. Animals were anesthetized and the basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values were recorded, and then the basilar artery was punctured, causing SAH. Blood was drawn to induce hypotension [60-70 mmHg mean arterial blood pressure (MABP)]. Control rats received intraperitoneal (i.p.) injections of 0.5 ml saline immediately after SAH before hypotension induction and after 60 min of occlusion. Experimental rats received 400-mg/kg citicoline i.p. at the same time points. Control group I and treatment group III were subjected to 60 min of interrupted occlusion (5 min of reperfusion after each 10 min of occlusion). Control group II and treatment group IV were subjected to 60 min of uninterrupted occlusion. MABP and LCBF were recorded every 5 minutes. Brain edema was evaluated in seven rats from each group at 24 hours after ischemic injury. At 3 days after occlusion, another set of 28 rats was killed and coronal brain slices were stained to assess infarct volume. The groups' physiological and edema findings were similar. In all groups, LCBF fell immediately after SAH and remained below baseline throughout the experiment. In the citicoline-treated rats, arterial pressure increased significantly after 30-40 min of occlusion, and brain slices showed significantly smaller infarct volumes compared to control slices (p < 0.05). Mortality was significantly lower in the citicoline-treated animals (p < 0.001). The results suggest that citicoline provides significant neuroprotection during cerebral ischemia, and that it significantly reduces mortality. Part of the neuroprotective effect may be mediated by recovery of arterial pressure.

An anatomical and pathological evaluation of middle cerebral artery occlusion in rats.

Adult male Sprague-Dawley rats (n = 87) weighing 350-400 g were used for studying the anatomy of the horizontal segment of middle cerebral artery and infarct area after occlusion of the artery. In the experimental group (n = 27) middle cerebral artery was coagulated 3-4 mm length from the origin of the lateral striate arteries to the inferior cerebral vein and divided. Control rats (n = 20) had all the surgical procedures except occlusion. Another group of rats (n = 40) were used to determine the anatomical variations of middle cerebral artery after intracarotid carbon black injection. Five major patterns of middle cerebral artery were observed and two of them were major and constituted 92.5% of rats. Twenty-four hours after middle cerebral artery occlusion, all animals were neurologically evaluated. On the third day after occlusion the brains were stained with 2%, 2,3,5-triphenyltetrozolium chloride. The area of infarction was assessed by computerized analysis method. In our study after determining the variations of the middle cerebral artery and its branches in our strain of rats, we were able to achieve 92.5% grade III and IV infarcted area.

Effects of fetal septal grafts on memory and learning performance with hippocampal acetylcholine and choline metabolism in fimbria transected rats.

Female Sprague-Dawley rats underwent aspirative lesion of the fimbria to produce septohippocampal disconnection. Two weeks after the lesion surgery, fetal septal grafts prepared from ventral forebrain of 13-15 days old fetuses of the same outbred strain were placed into the lesion cavity (grafted group). Three months after grafting, all rats were tested for spontaneous motor activity (SMA), step through passive avoidance (STPA) and in Morris' water maze (MWM). Six months after grafting, both basal and stimulated acetylcholine (ACh) and choline (Ch) release and their tissue levels were measured in ipsilateral hippocampal slices. Septohippocampal disconnection caused a significant impairment in Morris' water maze tasks, but did not alter spontaneous motor activity and step through passive avoidance. Fimbrial lesion, moreover, also declined both stimulated ACh release and tissue ACh levels in hippocampal slices. While lesion-induced change in Morris' water maze was ameliorated partially, declines in both stimulated ACh release and tissue ACh levels were raised to the control levels by fetal septal graft placed into the lesion cavity. These data show that grafted cholinergic neurons can work biochemically which may not result with a complete behavioral amelioration which is, in fact something more complex.

Secondary insults during intrahospital transport of neurosurgical intensive care patients.

Secondary insults occurring after injury have been prospectively assessed in seven head-injured patients who required intrahospital transfer to a computerized tomography unit for re-evaluation of their brain injury. During transportation the intracranial pressure, blood pressure, and arterial blood gases were monitored. A significant increase in intracranial pressure was observed during transport (p < 0.01). The conclusion is that patients should be ventilated and have appropriate sedation and analgesia. This could provide some protection against secondary insults.