Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as "reactive astrogliosis." Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions

Ecology of the Invasive Red Alga Gracilaria salicornia (Rhodophyta) on O'ahu, Hawai'i

The red alga Gracilaria salicornia (C. Agardh) E. Y. Dawson was introduced intentionally to two reefs on O'ahu, Hawai'i, in the 1970s for experimental aquaculture for the agar industry. Some 30 yr later, this species has spread from the initial sites of introduction and is now competing with native marine flora and fauna. The goals of this study were to quantify various aspects of G. salicornia ecology in Hawai'i in an effort to develop control or eradication tools. Experimental plots were established to determine cover and biomass of G. salicornia per square meter and to determine the amount of time and person hours needed to remove G. salicornia from these plots. Substantial amounts of G. salicornia become dislodged from the reef during large wave events and periodically become deposited onto the beach in front of the Waikiki Aquarium. Algal beach wash biomass was quantified and positive relationships were established between swell height and the amount of algae that washed up onto the beach in this location. We then quantified the ability of G. salicornia vegetative fragments to regrow after desiccation to determine if algal biomass stranded on shore survives the tidal cycle until being washed back out on the reef at high tide. Gracilaria salicornia was remarkably resistant to temperature, salinity, and chemical treatments examined as possible in situ control options. Herbivore preference tests showed that a native Gracilaria species is consumed far more frequently than the alien congener. Finally, large-scale community volunteer efforts were organized to remove drifting G. salicornia fragments from the reef area in front of the Waikiki Aquarium. Over 20,000 kg of alien algal fragments were removed from this location in five 4-hr cleanup events. However, based on G. salicornia growth rates, ability to fragment, physical tolerance, and low herbivory, it is clear that a large-scale dedicated effort will be needed to control this invasive species on Waikiki's reefs

Predictors of Intraspinal Pressure and Optimal Cord Perfusion Pressure After Traumatic Spinal Cord Injury.

BACKGROUND/OBJECTIVES: We recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPPopt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPPopt can be predicted using clinical factors instead of ISP monitoring. METHODS: Sixty-four TSCI patients, grades A-C (American spinal injuries association Impairment Scale, AIS), were analyzed. For 24 h after surgery, we monitored ISP and SCPP and computed SCPPopt (SCPP that optimizes pressure reactivity). We studied how well 28 factors correlate with mean ISP or SCPPopt including 7 patient-related, 3 injury-related, 6 management-related, and 12 preoperative MRI-related factors. RESULTS: All patients underwent surgery to restore normal spinal alignment within 72 h of injury. Fifty-one percentage had U-shaped sPRx versus SCPP curves, thus allowing SCPPopt to be computed. Thirteen percentage, all AIS grade A or B, had no U-shaped sPRx versus SCPP curves. Thirty-six percentage (22/64) had U-shaped sPRx versus SCPP curves, but the SCPP did not reach the minimum of the curve, and thus, an exact SCPPopt could not be calculated. In total 5/28 factors were associated with lower ISP: older age, excess alcohol consumption, nonconus medullaris injury, expansion duroplasty, and less intraoperative bleeding. In a multivariate logistic regression model, these 5 factors predicted ISP as normal or high with 73% accuracy. Only 2/28 factors correlated with lower SCPPopt: higher mean ISP and conus medullaris injury. In an ordinal multivariate logistic regression model, these 2 factors predicted SCPPopt as low, medium-low, medium-high, or high with only 42% accuracy. No MRI factors correlated with ISP or SCPPopt. CONCLUSIONS: Elevated ISP can be predicted by clinical factors. Modifiable factors that may lower ISP are: reducing surgical bleeding and performing expansion duroplasty. No factors accurately predict SCPPopt; thus, invasive monitoring remains the only way to estimate SCPPopt

Changing incidence of Achilles tendon rupture in Scotland: a 15-year study.

OBJECTIVE: To determine the incidence of Achilles tendon rupture in Scotland from 1980 to 1995. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Data were obtained from the National Health Service Information and Statistics Division and analyzed in terms of age- and gender-specific incidence rates and time trends by age group. PARTICIPANTS: A total of 4,201 patients with Achilles tendon ruptures occurring during the study period. MAIN OUTCOME MEASURES: Calculation of incidence and of seasonality. RESULTS: The overall incidence of Achilles tendon rupture increased from 4.7/100,000 in 1981 to 6/100,000 in 1994, with a peak in 1986. In men, the incidence rose from 6.3/100,000 to 7.3/100,000. In women, the increase in incidence was more pronounced, from 3/100,000 to 4.7/100,000. In men, peak incidence rate occurred in the 30- to 39-year age group, whereas in women, the peak age-specific incidence occurred in those aged 80 years and older, with a steady increase after age 60. There was no evidence of a seasonality effect in the rate of occurrence of Achilles tendon rupture. A bimodal distribution of age at time of Achilles tendon rupture was noted. CONCLUSION: There was a significant increase in the incidence of Achilles tendon rupture during the period from 1980 to 1995. This reflects the increased incidence of the injury noted in other Northern European countries

Cortical and vestibular stimulation reveal preserved descending motor pathways in individuals with motor-complete spinal cord injury.

OBJECTIVE: To use a combination of electrophysiological techniques to determine the extent of preserved muscle activity below the clinically-defined level of motor-complete spinal cord injury. METHODS: Transcranial magnetic stimulation and vestibular-evoked myogenic potentials were used to investigate whether there was any preserved muscle activity in trunk, hip and leg muscles of 16 individuals with motor-complete spinal cord injury (C4-T12) and 16 able-bodied matched controls. RESULTS: Most individuals (14/16) with motor-complete spinal cord injury were found to have transcranial magnetic stimulation evoked, and/or voluntary evoked muscle activity in muscles innervated below the clinically classified lesion level. In most cases voluntary muscle activation was accompanied by a present transcranial magnetic stimulation response. Furthermore, motor-evoked potentials to transcranial magnetic stimulation could be observed in muscles that could not be voluntarily activated. Vestibular-evoked myogenic potentials responses were also observed in a small number of subjects, indicating the potential preservation of other descending pathways. CONCLUSION: These results highlight the importance of using multiple electrophysiological techniques to assist in determining the potential preservation of muscle activity below the clinically-defined level of injury in individuals with a motor-complete spinal cord injury. These techniques may provide clinicians with more accurate information about the state of various motor pathways, and could offer a method to more accurately target rehabilitation

A shorter French course /

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Natural and targeted circuit reorganization after spinal cord injury.

A spinal cord injury disrupts communication between the brain and the circuits in the spinal cord that regulate neurological functions. The consequences are permanent paralysis, loss of sensation and debilitating dysautonomia. However, the majority of circuits located above and below the injury remain anatomically intact, and these circuits can reorganize naturally to improve function. In addition, various neuromodulation therapies have tapped into these processes to further augment recovery. Emerging research is illuminating the requirements to reconstitute damaged circuits. Here, we summarize these natural and targeted reorganizations of circuits after a spinal cord injury. We also advocate for new concepts of reorganizing circuits informed by multi-omic single-cell atlases of recovery from injury. These atlases will uncover the molecular logic that governs the selection of 'recovery-organizing' neuronal subpopulations, and are poised to herald a new era in spinal cord medicine

Lateral medullary vascular compression manifesting as paroxysmal hypertension.

Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been described as a possible cause of refractory essential hypertension. We present the case of a patient affected by episodes of severe paroxysmal hypertension, some episodes associated with vago-glossopharyngeal neuralgia. Classical secondary forms of hypertension were excluded. Imaging revealed a neurovascular conflict between the posterior inferior cerebellar artery (PICA) and the ventrolateral medulla at the level of the root entry zone of the ninth and tenth cranial nerves (CN IX-X REZ). A MVD of a conflict between the PICA and the RVLM and adjacent CN IX-X REZ was performed, resulting in reduction of the frequency and severity of the episodes. Brain MRI should be performed in cases of paroxysmal hypertension. MVD can be considered in selected patients