Development of Ovulatory Menstrual Cycles in Adolescent Girls.

Irregular menstrual cycles due to anovulation are well described in the first few years after menarche, but the normal developmental trajectory from anovulatory to mature ovulatory cycles during adolescence remains undefined. In this article we review the very limited understanding of this final stage of female reproductive axis development and discuss why additional research in this area is critical to the health of women.

Spontaneous recovery after controlled cortical impact injury is not impeded by intermittent administration of the antipsychotic drug risperidone.

Several preclinical studies have reported that daily administration of the antipsychotic drug (APD) risperidone (RISP) impedes recovery after traumatic brain injury (TBI). However, it is not known whether intermittent dosing would produce similar deleterious effects. The relevance of providing APDs intermittently is that not all patients in rehabilitation require daily treatments to manage TBI-induced agitation. Hence, the goal of the current study was to test the hypothesis that intermittent (vs. daily) administration of RISP would be less disturbing to motor and cognitive recovery after TBI. Anesthetized adult male rats were subjected to either a cortical impact of moderate severity or sham injury and then were randomly assigned to groups receiving intraperitoneal injections of vehicle (VEH; 1.0 mL/kg) or RISP (0.45 mg/kg) 1x, 3x, or 7x per week until the completion of behavioral testing, which consisted of motor and cognitive assessments on post-operative days 1-5 and 14-19, respectively. The group receiving RISP 7x week exhibited greater motor and cognitive impairment compared to those receiving RISP 1x or 3x per week, or VEH [p<0.05]. Moreover, no differences were observed between the intermittent RISP groups vs. VEH [p>0.05], which supports the hypothesis. A potential clinical ramification is that RISP may be safe to manage agitation after TBI, but only when used sparingly.

Albeit nocturnal, rats subjected to traumatic brain injury do not differ in neurobehavioral performance whether tested during the day or night.

Behavioral assessments in rats are overwhelmingly conducted during the day, albeit that is when they are least active. This incongruity may preclude optimal performance. Hence, the goal of this study was to determine if differences in neurobehavior exist in traumatic brain injured (TBI) rats when assessed during the day vs. night. The hypothesis was that the night group would perform better than the day group on all behavioral tasks. Anesthetized adult male rats received either a cortical impact or sham injury and then were randomly assigned to either Day (1:00-3:00p.m.) or Night (7:30-9:30p.m.) testing. Motor function (beam-balance/walk) was conducted on post-operative days 1-5 and cognitive performance (spatial learning) was assessed on days 14-18. Corticosterone (CORT) levels were quantified at 24h and 21days after TBI. No significant differences were revealed between the TBI rats tested during the Day vs. Night for motor or cognition (p's<0.05). CORT levels were higher in the Night-tested TBI and sham groups at 24h (p<0.05), but returned to baseline and were no longer different by day 21 (p>0.05), suggesting an initial, but transient, stress response that did not affect neurobehavioral outcome. These data suggest that the time rats are tested has no noticeable impact on their performance, which does not support the hypothesis. The finding validates the interpretations from numerous studies conducted when rats were tested during the day vs. their natural active period.

Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma.

Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2 receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5mg/kg) or QUE (10mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1-5 and cognitive function was evaluated with a Morris water maze task on days 14-19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p>0.05], but all were impaired vs. SHAM controls [p<0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p<0.05]. Moreover, the TBI+continuous HAL group performed worse than the TBI+continuous VEH, TBI+continuous QUE, and TBI+intermittent QUE groups [p<0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly.

The Therapeutic Efficacy of Environmental Enrichment and Methylphenidate Alone and in Combination after Controlled Cortical Impact Injury.

Environmental enrichment (EE) and methylphenidate (MPH) independently confer significant benefit to behavioral recovery after controlled cortical impact (CCI) injury. Given that combinational therapies may be more clinically translatable than monotherapies, the aim of the current study was to test the hypothesis that a combined treatment regimen of EE and MPH would provide greater therapeutic efficacy than either one alone. Anesthetized adult male rats received either a CCI of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing where they received either intraperitoneal (ip) MPH (5 mg/kg) or vehicle (VEH; 1.0 mL/kg; ip) beginning 24 h after injury and once daily for 19 days. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. No differences were observed in sham controls regardless of treatments, and thus their data were pooled. The traumatic brain injury (TBI)+EE+VEH and TBI+EE+MPH groups exhibited enhanced beam balance and beam walk performance relative to the TBI+STD+VEH group (p < 0.05), but did not differ from one another (p > 0.05). No effect of MPH treatment alone was observed in either motor task. In contrast, MPH improved spatial learning and memory when presented alone and also when combined with EE relative to VEH-treated STD controls (p < 0.05). In addition, both EE groups performed significantly better than the TBI+STD+MPH group (p < 0.05), but did not differ from one another (p > 0.05). These data replicate previous findings that both EE and MPH confer cognitive benefits after TBI and extend the findings by revealing that combining EE and MPH does not produce effects greater than either treatment alone, which does not support the hypothesis. The lack of an additive effect may be because of the robustness of the EE.

Abbreviated environmental enrichment confers neurobehavioral, cognitive, and histological benefits in brain-injured female rats.

Environmental enrichment (EE) promotes behavioral recovery after experimental traumatic brain injury (TBI). However, the chronic rehabilitation provided in the laboratory is not analogous to the clinic where physiotherapy is typically limited. Moreover, females make up approximately 40% of the clinical TBI population, yet they are seldom studied in brain trauma. Hence, the goal of this study was to test the hypothesis that abbreviated EE would confer neurobehavioral, cognitive, and histological benefits in brain injured female rats. Anesthetized rats received a cortical impact of moderate-to-severe injury (2.8mm tissue deformation at 4m/s) or sham surgery and then were randomly assigned to groups receiving standard (STD) housing or 4h, 6h, or 24h of EE daily. Motor function (beam-balance/walk and rotarod) was assessed on post-operative days 1-5 and every other day from 1 to 19, respectively. Spatial learning/memory (Morris water maze) was evaluated on days 14-19, and cortical lesion volume was quantified on day 21. No statistical differences were appreciated among the sham controls in any assessment and thus the data were pooled. All EE conditions improved motor function and memory retention, but only 6h and 24h enhanced spatial learning relative to STD (p<0.05). Moreover, EE, regardless of duration reduced cortical lesion volume (p<0.05). These data confirm that abbreviated EE confers robust neurobehavioral, cognitive, and histological benefits in TBI female rats, which supports the hypothesis and strengthens the utility of EE as a pre-clinical model of neurorehabilitation.

A Stereodivergent Approach for Accessing Both C2,8a-Syn and C2,8a-Anti Relative Stereochemical Manifolds in the Lepadin Family via a TiCL(4)-Promoted Aza-[3 + 3] Annulation.

Details in developing a stereodivergent approach to the lepadin family and establishing an entry to both C2,8a-syn and C2,8a-anti relative stereochemical manifolds through a common intermediate are described here. This works paves a foundation for constructing all members of the lepadin family, which consists of three subsets based on an array of interesting relative configurations. These efforts underline the prominence of aza-[3 + 3] annulation as a unified strategy in alkaloid synthesis.