Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures

Abstract

The basal ganglia is a group of subcortical nuclei that are involved in many neuronal pathways associated with emotional, motivational, associative, and cognitive functions. Injury to the basal ganglia can result in serious complication in movement, perception, or judgement. 53 Stroke in the basal ganglia is not as common as in the cortex. 5,9,15,44,50 Patients with injury to the basal ganglia and internal capsule may have hypotonia, flaccid paralysis, or persistently impaired balance and ambulation and therefore benefit less from therapy. 31 In addition, the basal ganglia can be involved in epileptic seizures 46 as a remote inhibitory control circuit; 17 consequently the basal ganglia has been suggested as a potential target for neuromodulatory and pharmacologic treatment of temporal lobe epilepsy. 27,36 Compared with those of rodents, the brains of NHP are structurally and functionally more similar to human brain and therefore are excellent models for stroke research. 12,13,39 NHP models of stroke have been developed by occluding the middle cerebral artery (MCA); in these models, the ischemic lesion generally targets the cortical areas of the MCA territory. In our experimental exploration of NHP stroke model, we performed MCA occlusion in 12 macaques (8 animals received permanent MCA occlusion; the remaining 4 animals underwent transient occlusion). One of the macaques with permanent MCA occlusion initially developed a focal infarct in the right basal ganglion and later exhibited seizure symptoms at 48 h after stroke. MRI is a robust means to examine stroke lesions in both clinical and preclinical studies. 3,4,41,51,56 In the present study, we used MRI to document the longitudinal evolution of the basal ganglia infarction in the rhesus macaque that developed seizures. Materials and Methods The subject described here is an adult Indian-origin rhesus macaque (Macaca mulatta; ID no. Rpf6; sex, female; weight, 11 kg; age, 14 y) that was born and reared at the Yerkes National Primate Research Center, an AAALAC-accredited facility. The animal received the interventional stroke surgical procedure as reported previously. 14,45,55 Briefly, to induce permanent infarction within the MCA territory in the right cerebral hemisphere, a microcatheter was navigated through a parent catheter to the targeted M2 and M3 branches of the MCA, which were occluded by using 4-0 silk suture segments (5 to 10 mm). After the occlusion was confirmed angiographically by using fluoroscopy, the catheters were removed from the femoral artery before moving the animal to MRI. Animal care during MRI and surgery. The animal was initially anesthetized with 3 to 5 mg/kg of tiletamine-zolazepam and then intubated and maintained under approximately 2.0% isoflurane anesthesia for the stroke surgery and 1% to 1.5% isoflurane during MRI scans. The subject was immobilized during surgery and MRI by using custom-built head holders. All major physiologic parameters were monitored and remained within normal ranges. 29 Occlusion of the MCA was identified by usi...

Neuroprotection by Exogenous and Endogenous Neuregulin-1 in Mouse Models of Focal Ischemic Stroke

“…N = 5 mice (2 males + 3 females) per treatment group Therefore, it is clinically significant that NRG-1 is equally neuroprotective in both mice and rats. Recently, we developed a novel, minimally invasive ischemic stroke model with young male rhesus macaques (Rodriguez-Mercado et al 2012) which has been replicated with similar results in aged female monkeys (Zhang et al 2015;Li et al 2018). This procedure reliably produced infarcts and resulted in discrete and limited neurobehavioral deficits, indicating the potential of this stroke model for chronic neuroprotection studies in the future.…”

MRI monitoring of macaque monkeys in neuroscience: Case studies, resource and normative data comparisons

“…Quantitative MRI data from a given human neurology case is often compared to other patients of the same type and to normative data, informing patient-specific diagnosis, treatment and decision-making, whenever the patient's results are well outside of normative distributions. While this approach is available for human patients, outside of MRI information from specific disease models (e.g., Parkinson's disease ( Luan et al., 2008 ), stroke ( Li et al., 2018 )), MRI monitoring more broadly for nonhuman primates on neuroscientific procedures is largely missing, and a resource and framework for sharing these type of data are needed, as noted by ( Bridge et al., 2019 ; Prescott and Poirier, 2020 ; Basso et al., 2021 ). However, if established such an approach and resource could be of substantial benefit for animal welfare and in support of biomedical and scientific advance.…”

“…For human clinical patients the literature provides a substantial amount of information on the types of scans that can be used, how they can be interpreted to inform diagnosis and how information in cases can be compared with normative data or with data from larger patient samples ( Bradley Jr, 1993 ). However, outside of studies using MRI to evaluate the effects of disease models (e.g., Parkinson's disease ( Luan et al., 2008 ), stroke ( Li et al., 2018 )), the same type of approach is not always available or used in work with research animals. Rarely are cases reported, and even when MRI data is available ( Sadoun et al., 2015 ; Doane et al., 2018 ) few groups share them ( Bridge et al., 2019 ).…”

The Impact of Pediatric Basal Ganglia Stroke on Mental Health in Children: Report of 2 Cases

“…The basal ganglia are a group of subcortical nuclei that are strongly interconnected with several brain areas, including, but not limited to, the cerebral cortex and the thalamus. 10 , 14 Parallel frontal to subcortical neuronal circuits that connect specific regions of the frontal cortex to the striatum, globus pallidus and the thalamus are implicated in neuropsychiatric disorders. 15 Although the main anatomical structures that are involved are similar, the anatomical positions of the circuits are segregated in the caudate, putamen, and other deep gray structures.…”

“… 18 Basal ganglia involvement in neuronal pathways connected with the prefrontal cortex may contribute to the pathogenesis of several disorders affecting mood regulation, such as depression, anxiety, OCD, and attention. 10 , 13 , 14 Murakami et al 4 proposed that post-stroke apathetic depression might be associated with the intracranial dopamine pathway since it includes projections to the bilateral striatum. The cortico-striatal-thalamic-cortical circuit is heavily involved in the development of Tourette syndrome, and it has been reported that dysfunction in this pathway is linked to OCD.…”