Use of Arterial Spin-Labeling in Patients with Aneurysmal Sub-arachnoid hemorrhage.

Delayed cerebral ischemia (DCI) due to cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has long been recognized as a major source of morbidity and mortality. Early detection of cerebral vasospasm and identification of patients who are likely to become symptomatic is crucial to guide aggressive medical and/or endovascular interventions. Magnetic resonance imaging using arterial spin-label (ASL) is a noninvasive mean for assessing cerebral blood flow and is based on direct magnetic labeling of arterial blood water protons. The diagnostic role of ASL in acute ischemic stroke, epilepsy, and neurodegenerative disorders has been explained in multiple studies but its ability to predict vasospasm in aSAH has not been published before. The purpose of this study is to highlight the diagnostic implications of different perfusion patterns of ASL in patients with aSAH which can be utilized to prevent DCI in such patients when other commonly used modalities are not available, contraindicated, or fail to detect vasospasm.

Seizure Prophylaxis in the Immediate Post-Hemorrhagic Period in Patients with Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Seizures are a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) and occur most commonly in the immediate posthemorrhagic period. Most commonly used antiepileptic drugs (AEDs) for seizure prophylaxis in aSAH include phenytoin and levetiracetam. There is no reliable data available on the safety and efficacy of restricting AED prophylaxis only till the aneurysm is secured. METHODS: We retrospectively chart reviewed patients admitted to our neurosciences intensive care unit (NICU) with aSAH during the past two years. Seizure incidence was studied in patients treated with phenytoin versus levetiracetam and in patients treated for 3-7 days vs. those where AED was discontinued immediately after aneurysm was secured. RESULTS: In 28 patients, AED prophylaxis was discontinued immediately after the aneurysm was secured, and in 21 patients, it was continued for 3-7 days. Of the 28 patients who received AED prophylaxis for less than or equal to two days, phenytoin was used in 20 patients and levetiracetam was used in eight patients. In patients receiving AED prophylaxis for 3-7 days, phenytoin was used in eight cases and levetiracetam was used in 13 cases. None of these patients had seizures reported during hospitalization or at three-month follow-up. CONCLUSION: Stopping the AED prophylaxis immediately after aneurysm coiling is not associated with increased risk of seizures. Seizures at presentation in patients with aSAH are not associated with development of epilepsy at three months. Both phenytoin and levetiracetam are well tolerated in patients with aSAH when limited to the immediate posthemorrhagic period.

Brief neonatal maternal separation alters extinction of conditioned fear and corticolimbic glucocorticoid and NMDA receptor expression in adult rats.

Neonatal maternal separation alters adult HPA axis responsiveness to stress, adult emotionality, and glucocorticoid receptor (GR) concentrations in forebrain regions such as hippocampus. To investigate effects of neonatal maternal separation on emotion regulation and its neural substrates, we assessed acquisition and extinction of conditioned fear in adult rats that underwent neonatal maternal separation. Corticolimbic structures including basolateral amygdala and medial prefrontal cortex are critical for acquisition and extinction of conditioned fear, and such learning is N-methyl-D-aspartic acid (NMDA) receptor-dependent. Thus, we used immunohistochemistry to assess expression of the GR and the NR1 subunit of the NMDA receptor in basolateral amygdala and medial prefrontal cortex. On postnatal days 2-14, pups underwent control rearing or maternal separation for 15 min per day. Fear conditioning and extinction in adulthood were then assessed in male rats. Rats received five tone-alone habituation trials, then seven tone/footshock pairings. After 1 h, rats received tone-alone extinction trials to criterion, and 15 recall of extinction trials the next day. Brains were processed for immunohistochemical labeling of GR and NR1, and staining was quantified. Brief maternal separation did not alter acquisition or initial extinction, but impaired extinction recall. Brief maternal separation did not alter GR or NR1 expression in basolateral amygdala. However, brief maternal separation increased GR and decreased NR1 expression specifically in the infralimbic region of medial prefrontal cortex, consistent with work implicating this area in extinction recall. Thus, brief maternal separation impaired extinction recall and altered GR and NR1 expression in its neural substrate in adults.

Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum.

Neonatal maternal separation alters learning and memory. Glucocorticoids also modulate adult learning and memory, and neonatal maternal separation alters forebrain glucocorticoid receptor (GR) concentrations. We used eyeblink classical conditioning to assess the effect of neonatal maternal separation on associative learning. We assessed delay eyeblink conditioning, GR expression, and total neuron number in the interpositus nucleus, a critical site of plasticity in eyeblink conditioning, in adult rats that had undergone either standard animal facilities rearing, handling for 15 min, or maternal separation for either 15 or 60 min per day on postnatal days 2-14. At 2-3 months of age, delay eyeblink classical conditioning was assessed. Brains were processed for GR immunohistochemistry, and GR expression in the interpositus nucleus was assessed using a computer-based densitometry system. Neuron counts and nuclear volumes were obtained from an alternate series of thionin-stained sections. Maternal separation significantly impaired eyeblink conditioning in male but not female rats. Handling and maternal separation did not significantly affect interpositus neuron number and volume. However, prolonged maternal separation significantly increased GR expression in the posterior interpositus in males, and increases were correlated with eyeblink conditioning. In female rats, maternal separation and handling did not significantly alter interpositus neuron number, volume, or GR protein expression, and GR expression did not correlate with eyeblink conditioning. Thus, neonatal maternal separation produces adult deficits in eyeblink conditioning and alterations in GR expression in its neural substrate in a sex-dependent manner.