Correlation between periinfarct DC shifts and ischaemic neuronal damage in rat

286

130

Summary: In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological im portance for determining the volume of the ischemic in farct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals, Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 ± 14% of control (mean ± SD; p < 0,05), tissue P02 de clined from 28 ± 4 to 21 ± 3 mm Hg (p < 0.05), and EEG power fell to -80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 ± 4.8 min occurred at irregular intervals, and EEG power gradually During the last years, several laboratories have been able to show that glutamate antagonists reduce the volume of ischemic infarcts (Ozyurt et aI. , 1988; Park et aI., 1988; Dirnagl et aI., 1990). The thera peutical effect could not be attributed to increased cerebral blood flow (Park et aI., 1989; Iijima et aI., 1992), indicating that molecular mechanisms are in volved. This observation is widely held to support an excitotoxic mechanism of brain infarcts in anal ogy to glutamate toxicity in vitro (Choi, 1985) and the phenomenon of delayed neuronal death in se lectively vulnerable brain regions following a period of global ischemia (Suzuki et aI., 1983). The com-

Section: Discussionmentioning

confidence: 99%

Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

Back

Kohno

Hossmann

1994

286

130

“…A downward trend in glucose concentration is maintained at 3 h ( þ : 180 versus 20 mins, t (paired) ¼ 3.075, P ¼ 0.0133), whereas lactate appears more stable. (Takano et al, 1996;Busch et al, 1996;Back et al, 1996), and do so incrementally (because infarct size is proportional to the number of PIDs; Mies et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…These events-periinfarct depolarisations (PIDs)-appear to arise principally at the edge of the core area and spread into the peri-infarct zone (Strong et al, 1996). A role for PIDs as a cause rather than simply as a marker of the progression of infarct growth has been indicated by the positive correlation between number of PID events and infarct size (Gill et al, 1992;Chen et al, 1993;Mies et al, 1993) and, critically, by the demonstration that induction of depolarisations within or adjacent to the penumbra can enlarge the infarct (Back et al, 1996;Busch et al, 1996;Takano et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Transient Changes in Cortical Glucose and Lactate Levels Associated with Peri-Infarct Depolarisations, Studied with Rapid-Sampling Microdialysis

Hopwood

Parkin

Bezzina

et al. 2005

114

Peri-infarct depolarisations (PIDs) contribute to infarct expansion in experimental focal ischaemia; furthermore, depolarisations propagate in the injured human brain. Glucose utilisation is increased under both conditions, and depletion of brain glucose carries a poor prognosis. We studied dynamics of cerebral glucose and lactate in relation to PID patterns in experimental stroke. The middle cerebral artery was occluded for 3 h in 23 cats under terminal chloralose anaesthesia. We used fluorescence imaging to detect occurrence of PIDs, and rapid-sampling online microdialysis (rsMD), coupled to a flow-injection assay, to examine changes in cerebral cortical extracellular glucose and lactate at intervals of 30 sec each. After 30 min' ischaemia, lactate had increased by 43.67s.d. 45.9 lmol/L, and stabilised in that range for 3 h. In contrast, glucose fell only slightly initially (11.979.7 lmol/L), but progressively decreased to a reduction of 56.7747.2 lmol/L at 3 h, with no evidence of stabilisation. There was a highly significant inverse relationship of frequency of PIDs with plasma glucose (Po0.001). The results also characterise a metabolic signature for PIDs for possible application in clinical work, and emphasise potential risks in the use of insulin to control plasma glucose in patients with brain injury.

“…A first-and critical-difference between CSD and PID events is that whereas CSD is accompanied by marked, but transient hyperaemia (Leão, 1944a;Lauritzen et al, 1982), perfusion (as measured by laser Doppler probe) may fall transiently in association with a PID (Back et al, 1994). Secondly, CSD is not associated with histologic evidence of cytotoxicity (Nedergaard and Hansen, 1988), whereas there is a clear, direct relationship of infarct size with number of PIDs during a period of ischaemia (Mies et al, 1993), and infarct size is the dependent variable (Takano et al, 1996;Busch et al, 1996;Back et al, 1996). A group of findings suggests that residual vasoreactivity in the penumbra is an important determinant of outcome in this cortical territory.…”

Section: Rationale For Use Of the Laser Speckle Methods In Stroke Modementioning

confidence: 99%

“…There is persuasive experimental evidence that the extent of an ischaemic cerebral cortical infarct is related to the number of spontaneous periinfarct depolarisations (PIDs) (Mies et al, 1993), and that infarct size is the dependent variable in this relationship (Takano et al, 1996;Busch et al, 1996;Back et al, 1996). Analysis of any changes in perfusion of the cortex that might accompany a PID has been severely limited by the lack of a quantitative method that has sufficient spatial and temporal sampling power to allow detection and analysis of any changes that occur.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Laser Speckle Flowmetry for Imaging Cortical Perfusion in Experimental Stroke Studies: Quantitation of Perfusion and Detection of Peri-Infarct Depolarisations

Strong

Bezzina

Anderson

et al. 2005

Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBF umb ). Values of ICT and CBF umb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT-and CBF umb -derived values of perfusion were closely correlated, with a high degree of significance (P < 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.