Escalating Mean Arterial Pressure in Severe Traumatic Brain Injury: A Prospective, Observational Study.

To investigate cerebral autoregulatory status in patients with severe traumatic brain injury (TBI), guidelines now suggest active manipulation of mean arterial pressure (MAP). There is a paucity of data, however, describing the effect on intracranial pressure (ICP) when MAP is raised. Consecutive patients with TBI requiring ICP monitoring were enrolled from November 2019 to April 2020. The MAP and ICP were recorded continuously, and clinical annotations were made whenever intravenous vasopressors were commenced or adjusted to defend cerebral perfusion pressure (CPP) targets. A significant change in MAP burden was defined as MAP >100min.mm Hg over 15 min. The primary outcome was the change in ICP burden over the same 15-min period. Bedside and clinical parameters were then compared between these groups. Twenty-eight patients were enrolled, providing 212 clinical events, of which 60 were deemed significant. Over the first 15 min, 65% were associated with a net negative ICP burden. A greater reduction in ICP burden was observed with events occurring in patients without a history of hypotension at scene (p = 0.016), after three days post-injury (p = 0.0018), and where the pressure-reactivity index (PRx) was <0.25 (p = 0.0005) or the ICP amplitude to CPP correlation coefficient (RAC) was <-0.10 (p = 0.0036) at the initiation of vasopressor changes. The ICP burden in the first 15 min was highly correlated with the next 15-min period. In patients with severe TBI requiring ICP monitoring, increasing MAP to pursue a CPP target was followed by a net negative ICP burden in approximately two-thirds of events. These data suggest a MAP challenge may be a useful adjunct in managing intracranial hypertension.

Binocular neurons in parastriate cortex: interocular 'matching' of receptive field properties, eye dominance and strength of silent suppression.

Spike-responses of single binocular neurons were recorded from a distinct part of primary visual cortex, the parastriate cortex (cytoarchitectonic area 18) of anaesthetized and immobilized domestic cats. Functional identification of neurons was based on the ratios of phase-variant (F1) component to the mean firing rate (F0) of their spike-responses to optimized (orientation, direction, spatial and temporal frequencies and size) sine-wave-luminance-modulated drifting grating patches presented separately via each eye. In over 95% of neurons, the interocular differences in the phase-sensitivities (differences in F1/F0 spike-response ratios) were small (≤ 0.3) and in over 80% of neurons, the interocular differences in preferred orientations were ≤ 10°. The interocular correlations of the direction selectivity indices and optimal spatial frequencies, like those of the phase sensitivies and optimal orientations, were also strong (coefficients of correlation r ≥ 0.7005). By contrast, the interocular correlations of the optimal temporal frequencies, the diameters of summation areas of the excitatory responses and suppression indices were weak (coefficients of correlation r ≤ 0.4585). In cells with high eye dominance indices (HEDI cells), the mean magnitudes of suppressions evoked by stimulation of silent, extra-classical receptive fields via the non-dominant eyes, were significantly greater than those when the stimuli were presented via the dominant eyes. We argue that the well documented 'eye-origin specific' segregation of the lateral geniculate inputs underpinning distinct eye dominance columns in primary visual cortices of mammals with frontally positioned eyes (distinct eye dominance columns), combined with significant interocular differences in the strength of silent suppressive fields, putatively contribute to binocular stereoscopic vision.

Phase sensitivities, excitatory summation fields, and silent suppressive receptive fields of single neurons in the parastriate cortex of the cat.

We have recorded single-neuron activity from cytoarchitectonic area 18 of anesthetized (0.4-0.7% isoflurane in 65% N2O-35% O2 gaseous mixture) domestic cats. Neurons were identified as simple or complex on the basis of the ratios between the phase-variant (F1) component and the mean firing rate (F0) of spike responses to optimized (orientation, direction, spatial and temporal frequencies, size) high-contrast, luminance-modulated, sine-wave drifting gratings (simple: F1/F0 spike-response ratios > 1; complex: F1/F0 spike-response ratios < 1). The predominance (~80%) of simple cells among the neurons recorded from the principal thalamorecipient layers supports the idea that most simple cells in area 18 might constitute a putative early stage in the visual information processing. Apart from the "spike-generating" regions (the classical receptive fields, CRFs), the receptive fields of three-quarters of area 18 neurons contain silent, extraclassical suppressive regions (ECRFs). The spatial extent of summation areas of excitatory responses was negatively correlated with the strength of the ECRF-induced suppression of spike responses. Lowering the stimulus contrast resulted in an expansion of the summation areas of excitatory responses accompanied by a reduction in the strength of the ECRF-induced suppression. The spatial and temporal frequency and orientation tunings of the ECRFs were much broader than those of the CRFs. Hence, the ECRFs of area 18 neurons appear to be largely "inherited" from their dorsal thalamic inputs. In most area 18 cells, costimulation of CRFs and ECRFs resulted in significant increases in F1/F0 spike-response ratios, and thus there was a contextually modulated functional continuum between the simple and complex cells.

Differential effects of TGF-ß and FGF-2 on in vitro proliferation and migration of primate retinal endothelial and Müller cells.

PURPOSE: During retinal development, the pattern of blood vessel formation depends upon the combined effects of proliferation and migration of endothelial cells, astrocytes and Müller cells. In this study, we investigated the potential for transforming growth factor-ß (TGF-ß) and fibroblast growth factor (FGF-2) to influence this process by regulating proliferation and migration of retinal endothelial and macroglial cells. METHODS: We assessed the effects of exogenous TGF-ß and FGF-2 on the proliferation and migration of cultured endothelial (RF/6A) and Müller cell (MIO-M1) lines. Cell proliferation was measured using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay over 72 hr. Cell migration was measured using a scratch-wound assay over 72 hr. RESULTS: Transforming growth factor-ß inhibited the proliferation of endothelial and Müller cells and inhibited the migration of Müller cells, but not endothelial cells, compared to untreated controls. Conversely, FGF-2 increased endothelial cell proliferation but inhibited endothelial cell migration. Fibroblast growth factor-2 increased migration of Müller cells but had little effect on proliferation except at higher concentrations (20 ng/ml). CONCLUSION: Taken together, these observations indicate that TGF-ß and FGF could work in concert to inhibit endothelial cell proliferation and migration, respectively; this may have implications for establishing and maintaining the avascular zone of primate fovea.