Risk of bias within included studies.

<p>Effect of (<b>A</b>) random allocation to treatment groups, (<b>B</b>) blinded induction of ischaemia and, (<b>C</b>) blinded assessment of outcome on improvement in neurobiological score. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison.</p

Treatment specific parameters of regional hypothermia experiments.

<p>Effect of (<b>A</b>) temperature range of hypothermia induction, (<b>B</b>) time of hypothermia administration, (<b>C</b>) duration of hypothermia and, (<b>D</b>) experimental cotreatment on the effect size reported within experiments employing regional hypothermia. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison. Each stratification accounts for a significant proportion of the heterogeneity observed between studies.</p

Model specific parameters of regional hypothermia experiments.

<p>Effect of (<b>A</b>) animal species, (<b>B</b>) anaesthetic, and (<b>C</b>) induction of injury used, on the effect size observed within experiments utilising regional hypothermia. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison. Each stratification accounts for a significant proportion of the heterogeneity observed between studies.</p

Publication bias.

<p>(<b>A</b>) Eggar regression showing publication bias within the included studies. (<b>B</b>) Funnel plot showing the regional data in black and the systemic data in grey. No additional studies were suggested by trim and fill analysis.</p

Line graph exploring the relationship between compressive duration and compressive pressure.

<p>(A) The association between the duration of compression producing severe neurological injury and the compressive pressure in those studies in which there was an initial injury to the spinal cord followed by compression. The data demonstrates a close correlation and again obeys a power law relationship (y = 829.06x^-0.459) with a linear distribution on a log-log plot of the variables (upper inset). (B) Power law (y = 144.62x^-0.248) relationship between compressive pressure and duration in studies employing an initial injury to the spinal cord followed by narrowing of the spinal canal to induce compression. These models had lower estimated pressures and longer durations of compression were necessary to produce paraplegia.</p

Heterogeneity within systemic hypothermia experiments.

<p>Effect of neurobehavioural scale used on effect size reported for experiments employing systemic hypothermia. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison. Each stratification accounts for a significant proportion of the heterogeneity observed between studies.</p

Meta-regression of functional (neurobehavioral) improvement versus compressive pressure (p=0.004).

<p>The size of each point reflects the precision of each comparison.</p

The change in effect size with (A) Region of injury, (B) Method of compression (Clip = aneurysm clip), (C) Neurobehavioural score (NDS = Neurologic deficit score; Olby = Olby score; Tarlov = Tarlov scale; Multiple = ≥2 behavioural tests; Motor = Motor test; BBB = Basso Beattie Bresnahan scale).

<p>The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison. Each stratification accounts for a significant proportion of the heterogeneity observed between studies. (D) Meta-regression of functional neurobehavioural improvement versus the time of final assessment (p=0.046). The size of each point reflects the precision of each comparison.</p

Effect size and 95% confidence intervals of the neurobehavioural assessments in the 79 experiments included in meta-analysis.

<p>The reference line represents the overall effect size of 35.1% with the gray shaded bar the 95% confidence intervals (27.5-42.8) of the global estimate.</p

Effect sizes of included publications.

<p>Scatter plot demonstrating the distribution of effect sizes (% improvement in neurobiological score) within the included publications (n = 16). Individual experiments that employed a regional cooling approach (n = 11) vs. a systemic cooling approach (n = 14) have been identified and plotted as separate subgroups. The shaded gray bar represents the 95% confidence limits of the global estimate. The vertical error bars represent the 95% confidence intervals for the individual estimates. The width of each bar reflects the log of the number of animals contributing to that comparison.</p