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

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Influence of PARP-1 Polymorphisms in Patients after Traumatic Brain Injury

Poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the cellular response to stress and DNA damage. However, excessive activity of PARP-1 exacerbates brain injury via NAD+ depletion and energy failure. The purpose of this study was to determine if tagging single nucleotide polymorphisms (tSNPs) covering multiple regions of the PARP-1 gene are related to outcome after traumatic brain injury (TBI) in humans. DNA from 191 adult patients with severe TBI was assayed for four tSNPs corresponding to haplotype blocks spanning the PARP-1 gene. Categorization as favorable or poor outcome was based on Glasgow Outcome Scale (GOS) score assigned at 6 months. PARP-1 enzyme activity was indirectly evaluated by quantifying poly-ADP-ribose (PAR)-modified proteins in cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay. In multiple logistic regression analysis controlling for age, initial Glasgow Coma Scale score, and gender, the AA genotype of SNP rs3219119 was an independent predictor of favorable neurologic outcome. This SNP tags a haplotype block spanning the automodification and catalytic domains of the PARP-1 gene. SNP rs2271347 correlated with CSF PAR-modified protein level. This SNP, which did not correlate with outcome, tags a haplotype block spanning the promoter region of the PARP-1 gene. We conclude that after severe TBI in humans, a PARP-1 polymorphism within the automodification-catalytic domain is associated with neurological outcome, while a polymorphism within the promoter region was associated with CSF PAR-modified protein level. These findings must be replicated in a prospective study before the relevance of PARP-1 polymorphisms after TBI can be established