Cytoarchitectural disruption of the superior colliculus and an enlarged acoustic startle response in the Tuba1a mutant mouse.

The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin heterodimer formation resulting in defective neuronal migration during development. The consequence of decreased neuronal motility is a fractured pyramidal cell layer in the hippocampus and wave-like perturbations in the cerebral cortex. Here, we extend our characterisation of this mouse investigating the laminar architecture of the superior colliculus (SC). Our results reveal that the structure of the SC in mutant animals is intact; however, it is significantly thinner with an apparent fusion of the intermediate grey and white layers. Birthdate labelling at E12.5 and E13.5 showed that the S140G mutation impairs the radial migration of neurons in the SC. A quantitative assessment of neuronal number in adulthood reveals a massive reduction in postmitotic neurons in mutant animals, which we attribute to increased apoptotic cell death. Consistent with the role of the SC in modulating sensorimotor gating, and the circuitry that modulates this behaviour, we find that Jenna mutants exhibit an exaggerated acoustic startle response. Our results highlight the importance of Tuba1a for correct neuronal migration and implicate postnatal apoptotic cell death in the pathophysiological mechanisms underlying the tubulinopathies.

Reactive hyperemia in skin after cardiopulmonary bypass.

OBJECTIVE: To study reactive hyperemia (RH) using a transcutaneous PO2/PCO2 combination electrode heated to 37 degrees C and tissue reflectance spectrophotometry in patients before and after cardiopulmonary bypass (CPB) to determine whether microcirculatory function of skin is altered. DESIGN: Prospective study. SETTING: Anesthesiology and critical care unit of a university hospital. PARTICIPANTS: Eight patients undergoing elective CPB under mild hypothermia. INTERVENTIONS: To produce RH, blood flow to the forearm was prevented by inflation of a cuff to 300 mmHg for an interval of 5 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements were obtained on the day prior to surgery (DPS), on the day of surgery (DOS) rewarmed to 37 degrees C in the intensive care unit (ICU), and on the first (POD 1) and the third postoperative days (POD 3). The following parameters were recorded: preocclusive baseline cutaneous PO2, and PCO2 (B-PtcO2, B-PtcCO2), and microvascular hemoglobin saturation (B-HbO2); postischemic peak of PtcO2, PtcCO2, and HbO2; and 10 minutes after release of the cuff occlusion posthyperemic PtcO2, PtcCO2, and HbO2. B-PtcO2 was 3.5 +/- 1.2 mmHg on DPS, 2.6 +/- 0.7 mmHg on DOS, 1.5 +/- 0.3 mmHg on POD 1, and 3.5 +/- 3.5 mmHg on POD 3. B-PtcCO2 increased significantly from 40.1 +/- 2.5 mmHg to 52.2 +/- 2.0 mmHg on DOS (p = 0.01) and to 48.9 +/- 3.6 mmHg on POD 1 (p = 0.02). On POD 3, B-PtcCO2 was 40.6 +/- 2.6 mmHg. B-HbO2 declined from a preoperative value of 42.4% +/- 8.6% to 37.1% +/- 14.7% on DOS and further to 21.7% +/- 4.8% on POD 1, which was significantly different (p = 0.03). On POD 3, B-HbO2 still remained lower (30.7% +/- 6.2%) compared with the preoperative value. RH (deltaPtcO2, deltaHBO2) was quantified as the differences between peak PtcO2, HBO2 and B-PtcO2, B-HBO2. DeltaPtcO2 was 13.0 +/- 2.3 on DPS, 11.3 +/- 2.9 on DOS, 12.6 +/- 2.6 on POD 1, and 11.5 +/- 3.5 on POD 3. DeltaHBO2 was 42.0 +/- 5.6 on DPS, 40.0 +/- 7.1 on DOS, 49.9 +/- 2.5 on POD 1, and 52.9 +/- 6.4 on POD 3. The elimination rate of carbon dioxide from skin (ECO2) was calculated as difference between peak PtcCO2 and PtcCO2 after 3 minutes of reperfusion divided by the difference between peak PtcCO2 and B-PtcCO2. ECO2 was 1.0 +/- 0.2 kPa/min on DPS, 0.7 +/- 0.1 kPa/min on DOS, and 0.8 +/- 0.1 kPa/min on POD 1 and POD 3. CONCLUSION: Cutaneous microcirculation assessed by RH is well preserved during the immediate postoperative period in patients undergoing uncomplicated coronary artery surgery with CPB.