✓ This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.
Mustafa K. Baskaya, Yingan Hu, David Donaldson, Mary Maley, A. Muralikrishna Rao, M. Renuka Prasad and Robert J. Dempsey
Aclan Doğgan, A. Muralikrishna Rao, Mustafa K. Başkaya, V. L. Raghavendra Rao, Jane Rastl, David Donaldson and Robert J. Dempsey
✓ Polyamines and N-methyl-d-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 µg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 ± 0.4% vs. 83.5 ± 0.4%, p < 0.05) and infarct volume (132 ± 14 mm3 vs. 168 ± 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 ± 0.4°C vs. 36.2 ± 0.2°C; 37.7 ± 0.4°C vs. 37.6 ± 0.6°C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.
Aclan Doğan, a. Muralikrishna Rao, Muştafa K. Baskaya, James Hatcher, Cuneyt Temiz, V. L. Raghavendra Rao and Robert J. Dempsey
Object. The possible role of the polyamine interconversion pathway on edema formation, traumatic injury volume, and tissue polyamine levels after traumatic brain injury (TBI) was studied using an inhibitor of the interconversion pathway enzyme, polyamine oxidase.
Methods. Experimental TBI was induced in Sprague—Dawley rats by using a controlled cortical impact device at a velocity of 3 m/second, resulting in a 2-mm deformation. Immediately after TBI was induced, 100 mg/kg of N1,N4-bis(2,3-butadienyl)-1,4-butanediamine 2HCl (MDL 72527) or saline was injected intraperitoneally. Brain water content and tissue polyamine levels were measured at 24 hours after TBI. Traumatic injury volume was evaluated using 2% cresyl violet solution 7 days after TBI occurred. The MDL 72527 treatment significantly reduced brain edema (80.4 ± 0.8% compared with 81.2 ± 1.2%, p < 0.05) and injury volume (30.1 ± 6.6 mm3 compared with 42.7 ± 13.3 mm3, p < 0.05) compared with the saline treatment. The TBI caused a significant increase in tissue putrescine levels at the traumatized site (65.5 ± 26.5 pmol/g in the cortex and 70.9 ± 22.4 pmol/g in the hippocampus) compared with the nontraumatized site (7 ± 2.4 pmol/g in the cortex and 11.4 ± 6.4 pmol/g in the hippocampus). The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduced by a mean of 60% with MDL 72527 treatment.
Conclusions. These results demonstrate, for the first time, that the polyamine interconversion pathway has an important role in the increase of putrescine levels after TBI and that the polyamine oxidase inhibitors, blockers of the interconversion pathway, can be neuroprotective against edema formation and necrotic cavitation after TBI.
Mustafa K. Başkaya, Richard Roberts and Richard S. Polin
Richard S. Polin, Volker A. Coenen, Carolyn Apperson Hansen, Peter Shin, Mustafa K. Baskaya, Anil Nanda and Neal F. Kassell
Object. Transluminal angioplasty has become a widely used adjunct therapy to medical management of symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH). Despite anecdotal reports of universal, angiographically confirmed reversal of vasospasm and high rates of clinical improvement, no rigorous examination of the efficacy of this procedure has been conducted. In this study the authors assess the efficacy of the aforementioned procedure.
Methods. Thirty-eight patients enrolled as part of the North American trial of tirilazad in aneurysmal SAH underwent transluminal angioplasty for symptomatic cerebral vasospasm. Fifty-three percent of these patients showed good recovery or moderate disability based on their 3-month Glasgow Outcome Scale score.
Among the 38 patients who underwent angioplasty, the severity and type of vasospasm, use of papaverine in addition to balloon angioplasty, timing of treatment, and dose of study drug did not have an effect on the outcome. The results of their neurological examinations improved in only four of the 38 patients immediately after the procedure. A conditional logistic regression analysis was performed in which these patients were compared with individuals matched for age, sex, dose of study drug, admission neurological grade, and modified Glasgow Coma Scale score at the time of angioplasty. No effect on favorable outcomes was found for this procedure.
Conclusions. Transluminal cerebral angioplasty is very effective in reversing angiographically confirmed vasospasm, and anecdotal reports of its clinical utility are numerous. However, in this report the authors conclude that its superiority to medical management for symptomatic cerebral vasospasm is questionable.
Mustafa K. Başkaya, Aclan Doğan, A. Muralikrishna Rao and Robert J. Dempsey
Object. Cytidine 5′-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI.
Methods. After anesthesia had been induced in Sprague—Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet—dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight–10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5′-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown.
Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.
Anil Nanda, David A. Vincent, Prasad S. S. V. Vannemreddy, Mustafa K. Baskaya and Amitabha Chanda
Object. The goal of this study was to determine whether drilling out the occipital condyle facilitates surgery via the far-lateral approach by comparing data from 10 clinical cases with that from studies of eight cadaver heads.
Methods. During the last 6 years at Louisiana State University Health Sciences Center—Shreveport, 10 patients underwent surgery via the far-lateral approach to the foramen magnum. Six of these patients harbored anterior foramen magnum meningiomas, one patient a dermoid cyst, two patients vertebral artery (VA) aneurysms, and an additional patient suffered from rheumatoid disease of the craniocervical junction. The surgical approach consisted of retromastoid craniectomy and C-1 laminectomy.
The seven tumors and the pannus of rheumatoid disease were completely excised, and the two aneurysms were clipped without drilling the occipital condyle. In one patient a chronic subdural hematoma was found 3 months after surgery, but no patient displayed any complication associated with surgery. It is significant that in no patient was a cerebrospinal fluid leak present. All patients experienced improved neurological function postoperatively.
To compare surgical visibility, eight cadaveric specimens (16 sides) were studied, including delineation of the VA and its segments around the craniocervical junction. Increase in visibility as a function of fractional removal of the occipital condyle was quantified by measuring the degrees of visibility gained by removing one third and one half of the occipital condyle. Removal of one third of the occipital condyle produced a mean increase of 15.9° visibility, and removal of one half produced a mean increase of 19.9°.
Conclusions. On the basis of their findings the authors conclude that removal of the occipital condyle is not necessary for the safe and complete resection of anterior intradural foramen magnum tumors.
Mustafa K. Başkaya and Roberto C. Heros
Roham Moftakhar, Howard A. Rowley, Aquilla Turk, David B. Niemann, Beverly Aagaard Kienitz, Jamie Van Gomple and Mustafa K. Başkaya
Digital subtraction (DS) angiography is the gold standard for detecting cerebral vasospasm after subarachnoid hemorrhage (SAH). Computed tomography (CT) perfusion is a recently developed modality for the evaluation of cerebral hemodynamics. This study was conducted to evaluate the potential of using CT perfusion to detect vasospasm in patients with SAH.
Fourteen patients between the ages of 41 and 66 years with aneurysmal SAH underwent 23 CT perfusion scans for suspected vasospasm. All patients underwent DS angiography within 12 hours of the CT perfusion scans. The presence of vasospasm on CT perfusion images was determined based on qualitative reading using color maps of mean transit time, cerebral blood flow, and cerebral blood volume as criteria. The presence or absence of vasospasm as retrospectively determined using CT perfusion was compared with DS angiography findings.
Of the 23 CT perfusion scans performed, 21 (91%) were concordant with angiography findings in predicting the presence or absence of vasospasm. In 15 of 23 scans, the presence of vasospasm was detected on CT perfusion scans and confirmed on DS angiography studies. In two cases, vasospasm was revealed on DS angiography but was not confirmed on CT perfusion. The degree of agreement between CT perfusion and DS angiography for detection of vasospasm was high (κ = 0.8, p < 0.0001).
Computed tomography perfusion is an accurate, reliable, and noninvasive method to detect the presence or absence of vasospasm. It can be used as a tool to help guide the decision to pursue DS angiography with the intent to treat vasospasm.
Mustafa K. Başkaya, Mark W. Kiehn, Azam S. Ahmed, Özkan Ateş and David B. Niemann
Arterial bypass is an important method of treating intracranial disease requiring sacrifice of the parent vessel. The conduits for extracranial–intracranial (EC–IC) bypass surgery include the superficial temporal artery, occipital artery, superior thyroid artery, radial artery, and saphenous vein (long or short). In an aging population with an increased prevalence of vascular disease, conduits for EC–IC bypass may be in short supply in some patients. Herein, the authors describe a case in which the descending branch of the lateral circumflex femoral artery (DLCFA) was utilized as a high-flow conduit for an EC–IC bypass.
This 22-year-old woman presented with irregular menstrual periods, secondary amenorrhea, and hypothyroidism. A giant intrasellar and suprasellar mass was found. Angiography confirmed a 3.5 × 2.1–cm fusiform aneurysm involving the cavernous and supraclinoid segments of the right internal carotid artery. A suitable radial artery conduit was not available. The DLCFA was harvested and anastomosed between the M2 segment of the middle cerebral artery and the external carotid artery.
Durable clinical and angiographic results were apparent at the 2-month follow-up.
The DLCFA's diameter and length were used successfully in a high-flow EC–IC bypass surgery. The DLCFA may be a good alternative to radial artery and saphenous vein grafts for an EC–IC bypass requiring high flow.