Abstract
BackgroundIt has long been known that an intrastriatal microinjection of the archetypal pro-inflammatory cytokine, interleukin-1beta (IL-1β), in juvenile rats induces a chronic reduction in the apparent diffusion coefficient (ADC) of tissue water on magnetic resonance imaging (MRI). Reduced ADC during acute cerebral ischaemia is an established indicator of metabolic failure whereas the cause of the IL-1β-induced reduction remains to be deciphered. Previously, it has been shown that IL-1β does not perturb the phosphorus (31P) magnetic resonance spectroscopy (MRS)-detectable energy status of an ex vivo preparation of rat brain parenchyma that is devoid of a functional vasculature component. However, brain energy status following an IL-1β challenge in vivo remains to be examined.MethodsThis study is the first longitudinal in vivo examination of the correlation of ADC MRI with localised 31P MRS signals obtained specifically from within the injected and non-injected striatum following IL-1β (1 ng/ul or 100 ng/ul) challenge, in real-time.ResultsDespite observing a chronic reduction in ADC at either dose of IL-1β challenge, energy compromise was not detected at any time point.ConclusionsThe IL-1β-induced effects pertaining to a functional vasculature such as leukocyte recruitment, blood–brain barrier (BBB) breakdown and blood flow changes are unlikely to impact on overall tissue energy status. Compared to classic ischaemia, there is dissociation between ADC and energy status within an IL-1β-induced lesion in vivo.
Highlights
It has long been known that an intrastriatal microinjection of the archetypal pro-inflammatory cytokine, interleukin-1beta (IL-1β), in juvenile rats induces a chronic reduction in the apparent diffusion coefficient (ADC) of tissue water on magnetic resonance imaging (MRI)
MRI Thresholding demonstrates a significantly reduced ADC that presents at 6 h and persists up to 72 h One-way analysis of variance (ANOVA) showed significant variation in ADC of the IL-1β-injected hemisphere (p = 0.0004), and posttesting using Bonferroni multiple comparisons test showed a significantly reduced ADC at 6 h (p < 0.01), 24 h (p < 0.001) and 72 h (p < 0.01) compared with 2.5 h (Fig. 1a and b)
With respect to the dimensions of the 31P magnetic resonance spectroscopy (MRS) voxel, the ADC change is significant at 24 h only, and returns to baseline by 72 h One-way ANOVA showed significant variation (p = 0.0034) in the ADC of tissue contained within the 31P MRS voxel
Summary
It has long been known that an intrastriatal microinjection of the archetypal pro-inflammatory cytokine, interleukin-1beta (IL-1β), in juvenile rats induces a chronic reduction in the apparent diffusion coefficient (ADC) of tissue water on magnetic resonance imaging (MRI). Intrastriatal microinjection of IL-1β in three-week-old (P21) juvenile rats induces a chronic reduction in the apparent diffusion coefficient (ADC) of tissue water on magnetic resonance imaging (MRI) [3]. This is indicative of a loss of high-energy phosphates, detectable using non-invasive phosphorus (31P) magnetic resonance spectroscopy (MRS), in experimental acute cerebral ischaemia [4,5,6]. A reduction in cerebral blood flow (CBF) promotes the failure of adenosine triphosphate (ATP)-dependent cell membrane ion pumps, dysregulating cell volume [for review, see [7], inducing cell swelling, reducing the extracellular space and, the ADC [8,9,10]
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