Delayed Striatal Neurodegeneration In Rats After A 15-minute Transient Focal Ischemia Studied By Magnetic Resonance Imaging And Spectroscopy

Cerebral ischemia (stroke) caused by blood vessel occlusion is one of the mostdevastating diseases affecting human health. It can result in severe behavioral andcognitive impairments(for example, vascular dementia) and even death. Magneticresonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are among themost important tools used in clinical and experimental stroke studies. Thesetechniques can be applied in the diagnostic, mechanistic and therapeutic aspects ofstroke. In fact, they have been used extensively in stoke studies to delineatemorphological/structural, hemodynamic and metabolic changes of the ischemiclesions, to monitor post-ischemia inflammatory response, to evaluate the efficacy ofthrombolytic treatment and other therapies, to discover functional reorganization ofthe central nervous system after stroke, and last but not least, to explore novel ideas ofregenerative therapies such as stem cell implantation.Previous studies have found that rats subjected to a 15-minute transient middlecerebral artery occlusion (MCAO) focal ischemia show neurodegeneration in thedorsolateral striatum only, and the resulting striatal lesion is associated with increasedT₁-weighted signal intensity and decreased T₂-weighted signal intensity at 2-8 weeksafter the initial ischemia. In this study, we investigated the possible mechanismsunderlying the delayed increase of T₁-weighted signal intensity in the ischemiclesions using MRI, in vivo ¹H MRS and synchrotron radiation X-ray fluorescence(SRXRF) elemental analysis. We observed that delayed (2 weeks after ischemia) increase in T₁-weighted signal intensity in the ischemic striatum is accompanied bysignificant increases in manganese, calcium and iron contents, but without evidentaccumulation of MRS-visible lipids or hydroxyapatite precipitation. The results showthat it is most likely that the increased deposition of paramagnetic manganesecontributed significantly to the delayed increase in T₁-weighted signal intensityobserved in the ischemic lesions.N-acetyl-aspartate (NAA), a metabolite visible to in vivo ¹H MRS, isconventionally considered to be exclusively located in neurons in the adult brain. Ithas been used as a specific marker for the integrity and viability of the neurons.Generally speaking, compared to normal tissue, ischemic lesions are often associatedwith low levels of NAA due to significant neuronal loss. However, recent studieshave shown that in a permanent MCAO ischemia model in rat, NAA level in theinfarcted area can recover to the control level at 30 days after ischemia. Using in vivo¹H MRS, we measured the temporal changes of NAA in the isehemic lesion after a15-minute MCAO ischemia. The results showed that the NAA level is acutelyreduced in the ipsilateral striatum, which recovers gradually, despite of the presenceof extensive selective neuronal death, to the control level by 2 weeks after ischemia.The mechanisms underlying NAA recovery remain to be investigated. However, ourresults raise questions regarding the validity of using NAA as a specific neuronalmarker in the chronic stage of stroke.