Long-term deficits in cortical circuit function after asphyxial cardiac arrest and resuscitation in developing rats

AbstractCardiac arrest is a common cause of global hypoxic-ischemic brain injury. Poor neurologic outcome among cardiac arrest survivors results not only from direct cellular injury but also from subsequent long-term dysfunction of neuronal circuits. Here, we investigated the long-term impact of cardiac arrest during development on the function of cortical layer IV (L4) barrel circuits in the rat primary somatosensory cortex. We used multielectrode single-neuron recordings to examine responses of presumed excitatory L4 barrel neurons to controlled whisker stimuli in adult (8 ± 2-mo-old) rats that had undergone 9 min of asphyxial cardiac arrest and resuscitation during the third postnatal week. Results indicate that responses to deflections of the topographically appropriate principal whisker (PW) are smaller in magnitude in cardiac arrest survivors than in control rats. Responses to adjacent whisker (AW) deflections are similar in magnitude between the two groups. Because of a disproportionate decrease in PW-evoked responses, receptive fields of L4 barrel neurons are less spatially focused in cardiac arrest survivors than in control rats. In addition, spiking activity among L4 barrel neurons is more correlated in cardiac arrest survivors than in controls. Computational modeling demonstrates that experimentally observed disruptions in barrel circuit function after cardiac arrest can emerge from a balanced increase in background excitatory and inhibitory conductances in L4 neurons. Experimental and modeling data together suggest that after a hypoxic-ischemic insult, cortical sensory circuits are less responsive and less spatially tuned. Modulation of these deficits may represent a therapeutic approach to improving neurologic outcome after cardiac arrest.</jats:p

Photochemistry of 2-methylcyclododecanone.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23069/1/0000643.pd

Thalamocortical dysfunction and thalamic injury after asphyxial cardiac arrest in developing rats

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic Reticular Nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on post-natal day 17. We found that 48–72 hours after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6–8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine min of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the Reticular Nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest

Photochemistry of 2-methylcycloalkanones

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23077/1/0000652.pd

Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children

Background: Inflammasome-mediated neuroinflammation may cause secondary injury following traumatic brain injury (TBI) in children. The pattern recognition receptors NACHT domain-, Leucine-rich repeat-, and PYD-containing Protein 1 (NLRP1) and NLRP3 are essential components of their respective inflammasome complexes. We sought to investigate whether NLRP1 and/or NLRP3 abundance is altered in children with severe TBI. Methods: Cerebrospinal fluid (CSF) from children (n = 34) with severe TBI (Glasgow coma scale score [GCS] ≤8) who had externalized ventricular drains (EVD) placed for routine care was evaluated for NLRP1 and NLRP3 at 0-24, 25-48, 49-72, and >72 h post-TBI and was compared to infection-free controls that underwent lumbar puncture to rule out CNS infection (n = 8). Patient age, sex, initial GCS, mechanism of injury, treatment with therapeutic hypothermia, and 6-month Glasgow outcome score were collected. Results: CSF NLRP1 was undetectable in controls and detected in 2 TBI patients at only 4 (15.50 [3.65-25.71] vs. 3.04 [1.52-8.87] ng/mL, respectively; p = 0.048). Controlling for initial GCS in multivariate analysis, peak NLRP3 >6.63 ng/mL was independently associated with poor outcome at 6 months. Conclusions: In the first report of NLRP1 and NLRP3 in childhood neurotrauma, we found that CSF NLRP3 is elevated in children with severe TBI and independently associated with younger age and poor outcome. Future studies correlating NLRP3 with other markers of inflammation and response to therapy are warranted

Two New Gravitationally Lensed Double Quasars from the Sloan Digital Sky Survey

We report the discoveries of the two-image gravitationally lensed quasars, SDSS J0746+4403 and SDSS J1406+6126, selected from the Sloan Digital Sky Survey (SDSS). SDSS J0746+4403, which will be included in our lens sample for statistics and cosmology, has a source redshift of z_s=2.00, an estimated lens redshift of z_l~0.3, and an image separation of 1.08". SDSS J1406+6126 has a source redshift of z_s=2.13, a spectroscopically measured lens redshift of z_l=0.27, and an image separation of 1.98". We find that the two quasar images of SDSS J1406+6126 have different intervening MgII absorption strengths, which are suggestive of large variations of absorbers on kpc scales. The positions and fluxes of both the lensed quasar systems are easily reproduced by simple mass models with reasonable parameter values. These objects bring to 18 the number of lensed quasars that have been discovered from the SDSS data.Comment: 25 pages, 6 figures, The Astronomical Journal accepte

Innate Gender-based Proclivity in Response to Cytotoxicity and Programmed Cell Death Pathway

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Detection of PHLPP1α/β in Human and Mouse Brain by Different Anti-PHLPP1 Antibodies

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal at ~150 kDa as evidenced by its abundance in PHLPP1 KO tissues. Results suggest Cosmo antibody is a better reagent to detect PHLPP1α by Western blot. In contrast, we found it unsuitable for immunofluorescence applications in brain. Our findings caution interpretation of the ~150 kDa band detected by some PHLPP1 antibodies in rodent and human tissues. Results also recapitulate the importance of including molecular weight standards in Western blot data to simplify retrospective analysis

Discovery of a Gravitationally Lensed Quasar from the Sloan Digital Sky Survey: SDSS J133222.62+034739.9

We report the discovery of the two-image gravitationally lensed quasar SDSS J133222.62+034739.9 (SDSS J1332+0347) with an image separation of Delta_theta=1.14". This system consists of a source quasar at z_s=1.445 and a lens galaxy at z_l=0.191. The agreement of the luminosity, ellipticity and position angle of the lens galaxy with those expected from lens model confirms the lensing hypothesis.Comment: 16 pages, 4 figures, the Astronomical Journal accepte