Israel Melamed

Cell-free DNA--a marker to predict ischemic brain damage in a rat stroke experimental model.

BackgroundThe animal model of stroke that is most frequently used is a rat model of focal brain ischemia caused by middle cerebral artery occlusion (MCAO). Several studies have reported a link between levels of cell-free DNA (CFD) and neurologic outcome in human stroke. The purpose of this study was to assess brain injury and measure CFD levels in 2 models of MCAO in rats, and to determine whether brain injury correlates with CFD. MethodsA total of 60 rats were used for this study. Twenty rats underwent a sham procedure, 20 rats had MCAO using a monofilament, and 20 rats had MCAO with a silicon-coated filament. Groups were further divided into 2 subgroups. In 1 subgroup of 10 rats, neurologic performance [measured as a neurologic severity score, (NSS)] was measured at 1 and 24 hours after the procedure, and brain edema and infarct volume were determined at 24 hours. In the second subgroup of 10 rats, CFD was measured at 0, 1, 2, 4, 8, 12, and 24 hours and at 2, 3, 4, and 5 days. Neurologic performance (measured as a NSS) was measured at 1 and 24 hours after the procedure. ResultsThe main finding was a significant increase in CFD levels observed 24 hours after the onset of MCAO. The correlation between the total infarct volume and CFD levels of the 3 groups was R=0.78, P<0.0001. Brain edema and NSS also were strongly correlated with CFD levels at 24 hours after MCAO (R=0.91, P<0.0001 and R=0.73, P<0.0001, respectively). ConclusionsWe found that CFD levels correlate well with the extent of ischemic injury, brain edema, and neurologic outcome in rats 24 hours post-MCAO. We have also shown that CFD correlates well with the expected temporal progression of ischemic injury. These findings place CFD in a unique place as a biomarker for stroke, both experimentally and possibly clinically.

Pyruvate’s blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms in a rat model of stroke

In previous studies, we have shown that by increasing the brain‐to‐blood glutamate efflux upon scavenging blood glutamate with either oxaloacetate or pyruvate, one achieves highly significant neuroprotection particularly in the context of traumatic brain injury. The current study examines, for the first time, how the blood glutamate scavenging properties of glutamate–pyruvate transaminase (GPT), alone or in combination with pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to brain ischemia, as they do after head trauma. Rats that were exposed to permanent middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg pyruvate had a smaller volume of infarction and reduced brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg glutamate had a worse neurological outcome and a larger extent of brain edema. The decrease in mortality, infarcted brain volume and edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood glutamate levels. We therefore suggest that the blood glutamate scavenging activity of GPT and pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of ischemic stroke.

The neuro-behavioral profile in rats after subarachnoid hemorrhage.

Despite significant advancements in the understanding of the pathophysiological mechanisms of subarachnoid hemorrhage (SAH), little is known about the emotional consequences. The primary goal of this study was to describe the locomotor and behavioral patterns in rats following both a single-injection and double-injection model of SAH. In 48 rats, SAH was induced by injecting 0.3 ml of autologous arterial blood into the cisterna magnum (single-hemorrhagic model). In 24 of these rats, post-SAH vasospasm was induced by a repeated injection of blood into the cisterna magnum 24h later (double-hemorrhagic model). In 24 additional rats, 0.3 ml of saline was injected into the cisterna magnum (sham group). Neurological performance was assessed at 24, 48 h, 1, 2 and 3 weeks after SAH. Four behavioral tests were performed for 3 weeks after SAH for the duration of 6 consequent days, in the following order: open field test, sucrose preference test, elevated plus maze test and forced swimming test. Following both, a single and double-hemorrhagic models of SAH, rats were found to have significant behavioral abnormalities on the open field test, sucrose preference test, elevated plus maze test, and forced swimming test. A more prominent disability was found in rats that underwent the double-hemorrhagic model of SAH than rats that underwent the single-hemorrhagic model. Both a single and double injection model of rats SAH are associated with significant behavioral disturbances including locomotor abnormalities, depressive behavior and increased anxiety, even as early as 3 weeks after SAH.

The role of hypothermia in the regulation of blood glutamate levels in naive rats.

Background: The exact mechanism of hypothermia-induced neuroprotection has not been determined yet; however, we hypothesized that it may be mediated by a blood glutamate–scavenging effect. Here, we examine the effect of hypothermic conditions (mild, moderate, and deep) on blood glutamate levels in naive rats. To identify the mechanism of hypothermia-induced glutamate reduction, we also measured concentrations of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), the primary regulators of glutamate concentration in blood. Methods: Rats were anesthetized with isoflurane, and their rectal temperature was maintained for 6 hours at 36 to 37°C, 33 to 36°C, 30 to 32°C, 18 to 22°C, or was not maintained artificially. At 6 hours, active cooling was discontinued and rats were allowed to rewarm. There were 12 rats in each group for a total of 60 rats. Blood samples were drawn at 0, 3, 6, 12, 24, and 48 hours for the determination of blood glutamate, GOT, and GPT levels. Results: A strong correlation between body temperature and blood glutamate levels was observed (P<0.001). Mild (33 to 36°C) and moderate (30 to 32°C) hypothermia led to reduced blood glutamate levels (P<0.001). Deep hypothermia (18 to 22°C) was associated with significant elevations in blood glutamate levels (P<0.001). Hypothermia, irrespective of the degree, led to elevations in GOT in plasma (P<0.001). Conclusions: Mild and moderate hypothermia led to a reduction in blood glutamate levels in rats, whereas deep hypothermia was associated with a significant elevation in blood glutamate levels. We further demonstrated an elevation of GOT and GPT levels, supporting their involvement in reducing blood glutamate by the conversion of glutamate to 2-ketoglutarate. We suggest that the neuroprotective properties of hypothermia may be partially because of a blood glutamate–scavenging mechanism.

Free craniotomy versus osteoplastic craniotomy, assessment of flap viability using 99mTC MDP SPECT.

There are currently two accepted neurosurgical methods to perform a bony flap. In an osteoplastic flap, the flap is attached to surrounding muscle. In a free flap, the flap is not attached to adjacent tissues. The former is less common due to its complexity and the extensive time required for the surgery; yet the rate of infection is significantly lower, a clear explanation for which is unknown. The objective of this study was to test the hypothesis that the osteoplastic flap acts as a live implant that resumes its blood flow and metabolic activity; contrasting with the free flap, which does not have sufficient blood flow, and therefore acts as a foreign body. Seven patients who underwent craniotomy with osteoplastic flaps and five with free flaps had planar bone and single photon emission computed tomography (SPECT) scans of the skull at 3-7days postoperative, after injection of the radioisotope, 99m-technetium-methylene diphosphonate (99m-Tc-MDP). We compared radioactive uptake as a measure of metabolic activity between osteoplastic and free flaps. Mean normalized radioactive uptakes in the centers of the flaps, calculated as the ratios of uptakes in the flap centers to uptakes in normal contralateral bone, were [mean: 1.7 (SD: 0.8)] and [0.6 (0.1)] for the osteoplastic and free flap groups respectively and were [2.4 (0.8)] and [1.3 (0.4)] in the borders of the flaps. Our analyses suggest that in craniotomy, the use of an osteoplastic flap, in contrast to free flap, retains bone viability.

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report

IntroductionThe Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.Case presentationWe present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patients condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.ConclusionsWe present a novel technique in which the Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.

A multidisciplinary approach for the treatment of young patients with suprasellar osteochondroma

BackgroundOsteochondroma is the most common benign bone tumor; intracranial osteochondroma is a very rare finding in the neurosurgical literature and most of them arise from the skull base.Case reportWe report a case of suprasellar ostheocondroma in a 16-year-old female, with its CT and MRI appearances, which caused visual deficits, resolved after surgery.DiscussionTo our knowledge, this is the fifth case of osteochondroma affecting the suprasellar region that has been reported, with all the characteristic features of this tumor: optic chiasmal syndrome, intralesional calcifications, cartilage cap, and contrast enhancement.ConclusionMultidiscplinary teams, including a neuro-ophthalmologist, endocrinologist, neuroradiologist, neurosurgeon, and neuropathologist are needed for correct treatment of the disease and appropriate follow-up.

Diagnosing necrotic meningioma: a distinctive imaging pattern in diffusion MRI and MR spectroscopy:

The differential diagnosis of necrotic meningiomas includes brain abscess and malignant neoplasms. We report and discuss hereby the work-up of two patients diagnosed with necrotic meningioma using diffusion-weighted imaging, magnetic resonance spectroscopy, resective surgery, and histopathology. The purpose of the present article is to add to the scant literature on the use of advanced imaging modalities in the routine investigation of brain lesions and their utility in arriving at the final diagnosis.