Longitudinal Changes in Resting-State Brain Activity in a Capsular Infarct Model

Abstract

Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[(18)F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC.

Remodeling of Neuronal Circuits After Reach Training in Chronic Capsular Stroke

“…We have previously demonstrated that microPET is a useful tool for assessing the longitudinal changes in restingstate brain activity (RSA) in a capsular infarct model. 11 In particular, microPET showed that SPRT training appeared to reduce cortical diaschisis and activate several subcortical structures, which presumably contributed to motor recovery. However, all animals received SPRT training in this previous study, so it was not clear whether these changes were the result of SPRT training, or the natural healing process, or a combination of both.…”

Is Remodelling of Corticospinal Tract Terminations Originating in the Intact Hemisphere Associated with Recovery following Transient Ischaemic Stroke in the Rat?

“…It must also be acknowledged that the motor dysfunction observed following MCAO may not have been solely attributed to loss of CST axons from the ischaemic hemisphere. For instance, the internal capsule has extensive subcortical-cortical connections within the affected hemisphere and between the two hemispheres and lesioning of the internal capsule results in depressed activity of these remote interconnected structures [ 33 ]. Thus, it cannot be ruled out that diaschisis contributed to the motor deficits and that the resolution of diaschisis participated in the functional recovery.…”

Enhanced Motor Recovery After Stroke With Combined Cortical Stimulation and Rehabilitative Training Is Dependent on Infarct Location

“…Endothelin-1 (0.2 μg/μL American Peptide, Sunnyvale) was delivered by the Nanolitre injection system (World Precision Instruments, Sarasota, Fl) using a SYS-Micro 4 Controller (World Precision Instruments, Sarasota, Fl). Stereotaxic coordinates of the injection site for MCAo were: anteroposterior, +0.9 mm; mediolateral, −5.2mm; and dorsoventral, −8.6 mm with respect to bregma 25 whereas for SCII were: anteroposterior, −3.0 mm; mediolateral, −3.0 mm; and dorsoventral, −7.0 mm with respect to bregma 11–12 . Doses of endothelin-1 were 3 μl for MCAo (240 pMol dissolved in 0.9% sterile saline) and1 μl for capsular injury (80 pMol dissolved in 0.9% sterile saline).…”

“…Ischemic damage was induced by injecting the vasoactive peptide endothelin-1 either onto the proximal branches of the middle cerebral artery (MCA) along the lateral aspect of the frontal cortex or into the subcortical territory within and surrounding the internal capsule, as previously described. 11,12,25 The hemisphere contralateral to each animal’s preferred reaching paw was targeted for injury. Animals were anesthetized with ketamine hydrochloride (70 mg/kg, intraperitoneally [ip]) and xylazine (5 mg/kg, ip), with supplemental isofluorane (0.15%) and ketamine (20 mg/kg, ip).…”

“…Stereotaxic coordinates of the injection site for MCA occlusion (MCAo) were anteroposterior, +0.9 mm; mediolateral, −5.2mm; and dorsoventral, −8.6 mm, with respect to bregma, 25 whereas for subcortical capsular ischemic injury (SCII), they were anteroposterior, −3.0 mm; mediolateral, −3.0 mm; and dorsoventral, −7.0 mm, with respect to bregma. 11,12 Doses of endothelin-1 were 3 µL for MCAo (240 pMol dissolved in 0.9% sterile saline) and1 µL for capsular injury (80 pMol dissolved in 0.9% sterile saline).…”