Three-dimensional ultrastructure of the brain pericyte-endothelial interface

Pericytes and endothelial cells share membranous interdigitations called “peg-and-socket” interactions that facilitate their adhesion and biochemical crosstalk during vascular homeostasis. However, the morphology and distribution of these ultrastructures have remained elusive. Using a combination of 3D electron microscopy techniques, we examined peg-and-socket interactions in mouse brain capillaries. We found that pegs extending from pericytes to endothelial cells were morphologically diverse, exhibiting claw-like morphologies at the edge of the cell and bouton-shaped swellings away from the edge. Reciprocal endothelial pegs projecting into pericytes were less abundant and appeared as larger columnar protuberances. A large-scale 3D EM data set revealed enrichment of both pericyte and endothelial pegs around pericyte somata. The ratio of pericyte versus endothelial pegs was conserved among the pericytes examined, but total peg abundance was heterogeneous across cells. These data show considerable investment between pericytes and endothelial cells, and provide morphological evidence for pericyte somata as sites of enriched physical and biochemical interaction.     

Lateralizing value of early head turning and ictal dystonia in temporal lobe seizures: a video-EEG study.

To investigate early head turning, we retrospectively studied videotapes of 262 seizures from 82 patients who were seizure free after temporal lobectomy. Early head movements were arbitrarily classified into non-tonic turning, tonic turning, and absence of turning. Among the 222 seizures which showed early head turning, 168 (75.7%) had non-tonic turning and 54 (24.3%) had tonic turning. The direction of the first head turning was ipsilateral to the epileptogenic foci in 132 (78.6%) seizures with non-tonic turning and in 35 (64.8%) seizures showing tonic head turning. The proportion of seizures with turning towards the ipsilateral side in the presence of tonic and non-tonic head turning were significantly different (P= 0.04). Seventy-four seizures (28.2%) evolved to secondary generalization, more frequently found in seizures with early head turning (P= 0.0015) and especially those showing tonic turning (P< 0.0001). The direction of head turning immediately preceding secondary generalization was contralateral to the lesion side in 53 seizures (82.8%). Dystonic upper limb posturing occurred in 86 seizures (32.8%), exclusively contralateral to the seizure focus, whereas 65 (75.6%) were associated with initial head turning ipsilateral to the focus. In summary, temporal lobe seizures with tonic head turning tends to secondarily generalize and the direction of head turning before secondarily generalized was contralateral to the seizure foci. Earlier in the seizures the direction of non-tonic head turning tends to be towards the epileptogenic hemisphere. In addition, dystonic posturing of the extremities is a significant lateralizing sign to the contralateral hemisphere in temporal lobe seizures.     

The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study

Bearden CE, Shih VH, Green MF, Gitlin M, Sokolski KN, Levander E, Marusak S, Hammen C, Sugar CA, Altshuler LL. The impact of neurocognitive impairment on occupational recovery of clinically stable patients with bipolar disorder: a prospective study.
Bipolar Disord 2011: 13: 323–333. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: Many patients with bipolar disorder do not regain their premorbid level of occupational functioning even after mood episodes have resolved. The reasons for this are not well understood. We evaluated the relationship between neurocognition and occupational function in bipolar disorder patients, following symptomatic recovery. Methods: A total of 79 previously employed adults with bipolar I disorder who achieved symptomatic recovery (i.e., at least six weeks clinically euthymic) following a manic episode underwent a neurocognitive evaluation and assessment of occupational functioning. Study participants were evaluated every three months thereafter for up to nine months. Factor analysis was applied to reduce the initial set of neurocognitive variables to five domains: episodic memory, working memory/attention, executive function, visual scanning, and speed of processing. Multiple logistic regression models were used to examine the joint predictive values of these domains for determining occupational recovery. Results: At the time of symptomatic recovery, four of five neurocognitive factors were significant predictors of concomitant occupational recovery and the fifth, executive function, showed a trend in the same direction. For those not occupationally recovered at baseline, longitudinal analyses revealed that changes between baseline and the three‐month follow‐up timepoint in most cognitive domains were robust and highly significant predictors of occupational recovery at three months. Conclusions: These findings indicate that better neurocognitive function in multiple domains and improvement in these domains over time are strongly predictive of subsequent occupational recovery. Treatments that target cognitive deficit may therefore have potential for improving long‐term vocational functioning in bipolar illness.     

Sustained Dyskinesias Following Elective Cessation and Reactivation of Chronic Subthalamic Nucleus Deep Brain Stimulation for a Surgical Procedure

Objectives: Subthalamic nucleus deep brain stimulation (STN DBS) is effective for treatment of levodopa‐induced dyskinesias in patients with Parkinson's disease (PD). Medical or surgical procedures requiring electrocautery may require inactivation of the pulse generators to avoid damage to the lead or extension wire or possible reprogramming of the stimulators. This generally causes only mild and temporary disability. We report a patient with previously well‐controlled dyskinesias who had severe and prolonged dyskinesias following reactivation of deep brain stimulation (DBS) following an orthopedic procedure. Materials and Methods: Retrospective chart review. Results: The patient underwent two orthopedic procedures, each requiring inactivation of DBS. After reactivation of DBS, the patient experienced severe dyskinesias that ultimately required sedation and ventilation to control large‐amplitude dyskinesias. Conclusions: Clinicians caring for PD patients treated with STN DBS should be aware of the possible reappearance of severe dyskinesias arising from routine inactivation and reactivation of pulse generators for medical or surgical procedures.     

Rearrangements of the MLL gene are influenced by DNA secondary structure,potentially mediated by topoisomerase II binding

The location of MLL translocation breakpoints within therapy‐related acute myeloid leukemia linked to drugs targeting Topoisomerase II and infant acute leukemia (IAL) are biased toward the intron 11–exon 12 region of MLL, although lacking a comprehensive explanation. To address this, blood samples were taken from breast cancer and lymphoma patients receiving Topoisomerase II inhibitor therapy. Inverse PCR analysis was used to interrogate the exon 12 region of MLL for rearrangements. Eleven of 19 observed translocations showed breakpoint junctions restricted to a single 5 bp location within exon 12. A similarly restricted distribution (11/20 breakpoint junctions) was observed in TK6 cells exposed to either estrogen (linked to IAL) or anti‐CD95 antibody. The translocation hotspot was at the 5′ edge of a 10‐bp tract matched with a perfect palindrome, 101 bp distant. A high stringency Topoisomerase II consensus sequence binding site was noted at the geometric midpoint of the palindromes. Ligation‐mediated PCR to screen TK6 cells exposed to anti‐CD95 antibody showed 14/37 (38%) of DNA breaks adjacent to the 5′ palindrome and 10/37 (27%) at the 3′ partner. We propose a model whereby Topoisomerase II facilitates the organization of nuclease‐sensitive secondary structures, stabilized by palindrome association, which are prone to rearrangement. © 2009 Wiley‐Liss, Inc.     

吡唑烷酮类化合物的抗惊厥作用

对3类14种吡唑烷酮类化合物的抗惊厥作用进行了比较研究,它们对最大电休克惊厥均有对抗作用,作用出现快,但维持时间较短,其中II-f作用最强,对听源性发作和家兔海马注射硫酸锌形成的慢性癫痫模型也有效。此外,III-类尚能对抗戊四唑引起的阵挛性惊厥。