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Aberrant expression or dysfunction of a number of genes in the brain contributes to epilepsy, a common neurological disorder characterized by recurrent seizures. Local overexpression of arachidonate lipoxygenase 3 (ALOXE3), a key enzyme for arachidonic acid (AA) metabolic pathway, alleviates seizure severities. However, the relationship between the ALOXE3 gene mutation and epilepsy has not been reported until now. Here we firstly characterized the promoter of human ALOXE3 gene and found that the ALOXE3 promoter could drive luciferase gene expression in the human HEK-293 and SH-SY5Y cells. We then screened the ALOXE3 promoter region and all coding exons from those patients with Dravet syndrome and identified 5 variants c.-163T > C, c.-50C > G, c.-37G > A, c. + 228G > A and c. + 290G > T in the promoter region and one missense variant c.1939A > G (p.I647 V) in the exon. Of these variants in the promoter region, only -50C > G was a novel variant located on the transcriptional factor NFII-I binding element. Luciferase reporter gene analyses indicated that the c.-50C > G could decrease gene expression by preventing the TFII-I's binding. In addition, the variant p.I647 V was conserved among all analyzed species and located within the ALOXE3 functional domain for catalyzing its substrate. In cultured cell lines, overexpression of ALOXE3 significantly decreased the cellular AA levels and overexpression of ALOXE3-I647 V could restore the AA levels, suggesting that the p.I647 V mutant led to a decrease in enzyme activity. Taken together, the present study proposes that the identified ALOXE3 variants potentially contribute to the AA-pathway-mediated epileptogenesis, which should provide a novel avenue for clinical diagnosis of epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The role of acyclovir for the treatment of herpes simplex encephalitis has been well documented, but the role of surgical decompression for herpes simplex encephalitis has only rarely been mentioned. The authors report two cases of herpes simplex encephalitis that involved surgical decompression., Case Description: In the first case, a therapeutic regimen of acyclovir was begun on the 11(th) day of the clinical course, and surgical decompression was performed because of impending uncal herniation on the 13(th) day. In the second case, a therapeutic regimen of acyclovir was begun on the third day of the disease's clinical course, and surgical decompression was performed because of impending uncal herniation on the 11(th) day. Both patients had good neurological outcomes and were seizure-free 12 months after their surgical procedures., Conclusion: We conclude that, for patients with herpes simplex encephalitis, it is important for the clinician to detect deterioration of consciousness because of the mass effect caused by the disease-associated inflammatory process as early as is possible. Surgical decompression is indicated for impending uncal herniation or intolerable increased intracranial pressure. Such surgery can contribute to an improved outcome for patients with herpes simplex encephalitis.

Background and Purpose: Hypertension is a major risk factor for ischemic and hemorrhagic stroke and may also cause more chronic and subtle brain injury. Progressive brain changes in a rat model of renal hypertension have been assessed to better understand the pathogenesis of hypertensive brain damage., Methods: Young adult rats were made hypertensive by partial occlusion of both renal arteries. MR images of brain were obtained weekly, and histopathological outcome was assessed. A separate group of rats was used to measure brain specific gravity and Evans blue dye content as an indicator of extravasation., Results: Rats developed maximal mean systolic blood pressures of 173 to >300 mm Hg, reaching a plateau in 6 to 8 weeks. Rats whose mean systolic pressure never exceeded 210 mm Hg never had brain lesions, while rats whose mean systolic pressure exceeded 276 mm Hg consistently developed brain lesions. Brain T2 values increased with increasing blood pressure. Lesions seen on MRI corresponded to those seen histologically. MRI also demonstrated transient brain expansion, probably due to diffusely increased water content, and rarely demonstrated focal cortical edema, which had no histological correlate. These transient phenomena, as well as hemorrhagic and ischemic infarcts, occurred mainly during the phase of climbing blood pressure and early stages of stable hypertension., Conclusions: Serial MRI reveals aspects of hypertensive brain disease that cannot be studied by histological examination alone. The observed phenomena are likely related to loss of autoregulation and/or blood-brain barrier integrity. Breach of blood vessel integrity is less likely once the vessels become accustomed to high pressures.

Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.