Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model - PubMed (original) (raw)

Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model

Juergen Bardutzky et al. J Cereb Blood Flow Metab. 2005 Aug.

Abstract

Dimethyl sulfoxide (DMSO) has a variety of biological actions that suggest efficacy as a neuroprotectant. We (1) tested the neuroprotective potential of DMSO at different time windows on infarct size using 2,3,5-triphenyltetrazolium staining and (2) investigated the effects of DMSO on ischemia evolution using quantitative diffusion and perfusion imaging in a permanent middle cerebral artery occlusion (MCAO) model in rats. In experiment 1, DMSO treatment (1.5 g/kg intravenously over 3 h) reduced infarct volume 24 h after MCAO by 65% (P<0.00001) when initiated 20 h before MCAO, by 44% (P=0.0006) when initiated 1 h after MCAO, and by 17% (P=0.11) when started 2 h after MCAO. Significant infarct reduction was also observed after a 3-day survival in animals treated 1 h after MCAO (P=0.005). In experiment 2, treatment was initiated 1 h after MCAO and maps for cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were acquired before treatment and then every 30 mins up to 4 h. Cerebral blood flow characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the ADC-derived lesion volume essentially stopped progressing during DMSO treatment, resulting in a persistent diffusion/perfusion mismatch. This effect was mainly observed in the cortex. Our data suggest that DMSO represents an interesting candidate for acute stroke treatment.

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Figures

Figure 1

Figure 1

2,3,5-Triphenyltetrazolium chloride (TTC) -defined corrected infarct volume 24 or 72 h after permanent middle cerebral artery occlusion (MCAO). Data are expressed as mean ±s.d. *P<0.01; **P<0.001; ***P<0.00001.

Figure 2

Figure 2

Representative apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) maps from one control and one dimethyl sulfoxide (DMSO)-treated animal subjected to permanent middle cerebral artery occlusion (MCAO). Three of eight maps are shown at 45 mins (baseline), 120, 180, and 240 mins after occlusion for ADC maps, and at 45 mins for CBF maps. Dimethyl sulfoxide treatment was initiated 1 h after occlusion.

Figure 3

Figure 3

(A) Temporal evolution of total apparent diffusion coefficient (ADC)- and cerebral blood flow (CBF)-derived lesion volumes (mean±s.d.) by using previously validated viability thresholds in permanently occluded rats. Dimethyl sulfoxide (DMSO) or saline infusion was initiated 1 h after occlusion. Saline group: CBF-lesion=closed diamonds, ADC-lesion= closed squares, 2,3,5-triphenyltetrazolium chloride (TTC)-lesion=gray square; DMSO group: CBF-lesion=open triangles, ADC-lesion=open circles, TTC-lesion=gray circle. (B) Temporal evolution of cortical and subcortical ADC lesion volumes (mean±s.d.). Saline lesion: cortex=closed circles, subcortex =closed squares; DMSO lesion: cortex=open circles, subcortex=open squares. *P<0.05 for differences in ADC lesion volumes at same time points. **_P_=0.002 for difference in TTC lesion volume at 24 h after occlusion.

Figure 4

Figure 4

Temporal evolution of apparent diffusion coefficient (ADC) (A) and cerebral blood flow (CBF) (B) in the core and mismatch regions defined before treatment (45 mins) in permanently occluded rats. Dimethyl sulfoxide (DMSO) or saline was administered 1 h after occlusion. Dimethyl sulfoxide group: core=open triangle, mismatch=open circles. Saline group: core=closed triangles, mismatch=closed circles. *P<0.05; **P<0.01; ***P<0.001.

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