Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome.

OBJECTIVES: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. DESIGN: Controlled, randomized, double-blinded laboratory study. SETTING: Animal research laboratories. SUBJECTS: Adult Wistar male rats (n = 110). INTERVENTIONS: Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed. MEASUREMENTS AND MAIN RESULTS: After argon inhalation for 24 hours immediately following "severe permanent ischemia" induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed. CONCLUSIONS: Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.

Early withdrawal of non-anesthetic antiepileptic drugs after successful termination of nonconvulsive seizures and nonconvulsive status epilepticus.

PURPOSE: Multiple antiepileptic drugs (AEDs) are often necessary to treat nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE). AED polypharmacy places patients at risk for adverse side effects and drug-drug interactions. Identifying the likelihood of seizure relapse when weaning non-anesthetic AEDs may provide guidance in the critical care unit. METHOD: Ninety-nine adult patients with successful treatment of electrographic-proven NCS or NCSE on continuous critical care EEG (CCEEG) monitoring were identified retrospectively. Patients were determined to undergo an AED wean if the number of non-anesthetic AEDs was reduced at the time of discharge compared to the number of non-anesthetic AEDs at primary seizure cessation. Primary outcome was recurrent seizures either clinically or by CCEEG during hospitalization. Secondary outcome measures included hospital length of stay and discharge disposition. RESULTS: The rate of recurrent seizures in the wean group was not statistically different when compared to the group that did not undergo an AED wean (17% vs. 13%, respectively; p = 0.77). The wean group had a median value of 4 (IQR: 3-4) non-anesthetic AEDs at the time of primary seizure cessation compared with 3 (IQR: 2-3) in the non-wean group (p < 0.0001). However, both groups had similar values of AEDs at discharge (median of 2 (IQR: 2-3) vs. 3 (IQR: 2-3) for wean and non-wean groups respectively; p = 0.40). Discharge disposition (favorable, acceptable, or unfavorable) was similar between groups (p = 0.32). CONCLUSIONS: Early weaning of non-anesthetic AEDs does not increase the risk of recurrent seizures in patients treated for NCS or NCSE during their hospitalization.

Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function.

Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function.