Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke

Abstract

Acute hyperglycaemia and chronic hypertension worsen stroke outcome but their impact on collateral perfusion, a determinant of penumbral life span, is poorly understood. Laser-speckle contrast imaging (LSCI) was used to determine the influence of these stroke comorbidities on cortical perfusion after permanent middle cerebral artery occlusion (pMCAO) in spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar rats. Four independent studies were conducted. In animals without pMCAO, cortical perfusion remained stable over 180 min. Following pMCAO, cortical perfusion was markedly reduced at 30 min then gradually increased, via cortical collaterals, over the subsequent 3.5 h. In the contralateral non-ischaemic hemisphere, perfusion did not change over time. Acute hyperglycaemia (in normotensive Wistar) and chronic hypertension (SHRSP) attenuated the restoration of cortical perfusion after pMCAO. Inhaled nitric oxide did not influence cortical perfusion in SHRSP following pMCAO. Thus, hyperglycaemia at the time of arterial occlusion or pre-existing hypertension impaired the dynamic recruitment of cortical collaterals after pMCAO. The impairment of collateral recruitment may contribute to the detrimental effects these comorbidities have on stroke outcome.

Keywords: Acute hyperglycaemia; cortical collateral perfusion; hypertension; ischaemic stroke; laser speckle contrast imaging; rat.

Figure 1.

Laser speckle contrast imaging set up and analysis. (a) A representative laser speckle image showing normally perfused rat brain with superior cortical vessels before pMCAO was induced. (b) A representative laser speckle image of the cortical surface following pMCAO, showing normal blood flow in the contralateral hemisphere (red–yellow) and cortical blood flow deficit in the ipsilateral hemisphere (blue–black). (c) ROIs on the LSCI defined with applied CBF thresholds: ischaemic core (cortical blood flow < 43% of mean contralateral hemisphere), hypoperfused tissue (cortical blood flow between 43 and 75% of mean contralateral hemisphere) along with contralateral equivalent ROIs.

Figure 2.

Recruitment of cortical collateral blood flow post-MCAO. (a) Cortical blood flow map of a representative rat per group. (b) Increase in cortical blood flow in the ROIs of the ipsilateral hemisphere following pMCAO, while blood flow remained relatively unchanged in the non-stroke control group over time. Cortical blood flow values for each ROI were normalised to their respective 10 min average at baseline and the entire ipsilateral hemisphere was the ROI for non-stroke controls. (c) Area under the curve of cortical perfusion in the ipsilateral hemisphere ROIs used to test the statistical difference between groups over the time course of ischaemia (0.5–4 h) and analysed using Student's unpaired t-test, p > 0.05*. (d) Cortical blood flow was unchanged from baseline in all equivalent ROIs in the contralateral hemisphere. (e) Area under the curve for cortical perfusion in the contralateral hemisphere ROIs, over the time course of ischaemia. (f) No significant change in MABP over the time course of the experiment. Area under the curve data for cortical perfusion presented as mean ± SD, other data presented as mean + SD.

Figure 3.

Impact of acute hyperglycaemia on cortical collateral blood flow. (a) Cortical blood flow map of a representative rat per group. (b) Cortical blood flow in the ipsilateral ischaemic core ROI. (c) Area the under curve for cortical perfusion (0.5–4 h) in the ipsilateral ischaemic core ROI of vehicle and glucose groups, p > 0.05*. (d) Cortical blood flow in the ipsilateral hypoperfused ROI. (e) Area under the curve of cortical perfusion (0.5–4 h) in the ipsilateral hypoperfused ROI. (f) Cortical perfusion in the ROI contralateral to ischaemic core. (g) Area under the curve of cortical perfusion in the ROI contralateral to ischaemic core, p > 0.05*. (h) Cortical perfusion in the ROI contralateral to the hypoperfused ROI. (i) Area under the curve of cortical perfusion in the ROI contralateral to the hypoperfused ROI, p > 0.05*. (j) MABP was stable during ischaemia, in vehicle and glucose groups. (k) Blood glucose concentration 10 min prior to and during ischaemia. Data were analysed using repeated measures two-way ANOVA, p = 0.0001*. Area under the curve data for cortical perfusion presented as mean ± SD, other data presented as mean + SD.

Figure 4.

Impact of chronic hypertension on cortical collateral blood flow. (a) Cortical blood flow map of a representative SHRSP rat following pMCAO. (b) Cortical blood flow normalised to the respective 10 min average at baseline in the ipsilateral ischaemic core and equivalent contralateral ROI. (c) Area under the curve of cortical perfusion in the ipsilateral ischaemic core and equivalent contralateral ROI, over the time course of ischaemia (0.5–4 h), analysed using Student's unpaired t-test, p > 0.05*. (d) Cortical blood flow, normalised to the respective 10 min average at baseline, in hypoperfused ROI and equivalent contralateral ROI. (e) Area under the curve of cortical perfusion for hypoperfused ROI and equivalent contralateral ROI. (f) MABP data over the time course of ischaemia. Area under the curve data for cortical perfusion presented as mean ± SD, other data presented as mean + SD.

Figure 5.

Influence of iNO on cortical collateral recruitment post-MCAO. (a) Cortical blood flow map for representative rat per group over the time course of ischaemia. (b) Cortical blood flow, normalised to the respective 10 min average at baseline, in the ipsilateral ischaemic core ROI. (c) Area under the curve of cortical perfusion in the ipsilateral ischaemic core ROI over the time course of ischaemia (0.5–4 h). (d) Cortical blood flow, normalised to the respective 10 min average at baseline, in the ipsilateral hypoperfused ROI. (e) Area under the curve for cortical perfusion in the ipsilateral hypoperfused ROI. (f) Cortical perfusion, normalised to the respective 10 min average at baseline, in the ROI contralateral to ischaemic core. (g) Area under the curve of cortical perfusion for ROI contralateral to ischaemic core. (h) Cortical perfusion, normalised to the respective 10 min average at baseline, in the ROI contralateral to hypoperfused ROI. (i) Area under the curve of cortical perfusion for ROI contralateral to hypoperfused ROI. (j) MABP over the time course of ischaemia in air and iNO groups. (k) Blood glucose concentration 10 min prior to and during the time course of ischaemia. Area under the curve data for cortical perfusion presented as mean ± SD, other data presented as mean + SD.