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Gross anatomical view of icv-STZ monkey brains. Representative superior, inferior, left, and right views (A, left to right) showing no focal lesion, no asymmetric alteration, and normal pattern of gyri and sulci in icv-STZ monkeys (A, C614), compared to controls (A, C529). Coronal sections at the level of the amygdala (B, #7; the seventh slice from rostral to caudal 4-mm cut) and hippocampus (B, #8-10) showing severe dilation of the lateral ventricles (arrows) and third ventricle (arrowhead) in icv-STZ monkeys (B, C614-C517) compared to controls (B, C529). C614, C517, and C529 indicate identification numbers for each monkey. Scale bar = 1 cm. Am, amygdala; Hip, hippocampus.
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In line with recent findings showing Alzheimer's disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-h...
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... 1). To investigate histopathological changes in the icv-STZ monkey brains, we collected the brains after fixation and compared their gross morphology with that of the control group. The representative superior, inferior, left, and right views were illustrated, showing no focal lesion, no asymmetric alteration, and normal pattern of gyri and sulci (Fig. 3A). The whole brains were cut into slices at coronal planes with 4 mm-thickness and the slices numbered 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). ...
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... inferior, left, and right views were illustrated, showing no focal lesion, no asymmetric alteration, and normal pattern of gyri and sulci (Fig. 3A). The whole brains were cut into slices at coronal planes with 4 mm-thickness and the slices numbered 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). These coronal slices showed severe dilation of the lateral ventricles (Fig. 3B, arrows) and third ventricle (Fig. 3B, Fig. 4. A deposition in microvessels and parenchyma. Paraffin-embedded sections of the ...
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... no focal lesion, no asymmetric alteration, and normal pattern of gyri and sulci (Fig. 3A). The whole brains were cut into slices at coronal planes with 4 mm-thickness and the slices numbered 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). These coronal slices showed severe dilation of the lateral ventricles (Fig. 3B, arrows) and third ventricle (Fig. 3B, Fig. 4. A deposition in microvessels and parenchyma. Paraffin-embedded sections of the brain slice #5 and #7 (left panel) were immunostained with A ...
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... of gyri and sulci (Fig. 3A). The whole brains were cut into slices at coronal planes with 4 mm-thickness and the slices numbered 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). These coronal slices showed severe dilation of the lateral ventricles (Fig. 3B, arrows) and third ventricle (Fig. 3B, Fig. 4. A deposition in microvessels and parenchyma. Paraffin-embedded sections of the brain slice #5 and #7 (left panel) were immunostained with A monoclonal antibody. Control brains exhibited minimal or no ...
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... 4 mm-thickness and the slices numbered 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). These coronal slices showed severe dilation of the lateral ventricles (Fig. 3B, arrows) and third ventricle (Fig. 3B, Fig. 4. A deposition in microvessels and parenchyma. Paraffin-embedded sections of the brain slice #5 and #7 (left panel) were immunostained with A monoclonal antibody. Control brains exhibited minimal or no immunoreactivity for A (data not shown), whereas the icv-STZtreated brains had prominent A ...
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... 7 to 10 (rostral to caudal), which contained temporal lobes, were chosen for further analysis (Fig. 3B). Slice number 7 was at the level of the amygdala (Fig. 3B, #7) and the others were at the level of hippocampus (Fig. 3B, #8 ∼ #10). These coronal slices showed severe dilation of the lateral ventricles (Fig. 3B, arrows) and third ventricle (Fig. 3B, Fig. 4. A deposition in microvessels and parenchyma. Paraffin-embedded sections of the brain slice #5 and #7 (left panel) were immunostained with A monoclonal antibody. Control brains exhibited minimal or no immunoreactivity for A (data not shown), whereas the icv-STZtreated brains had prominent A deposition in the longitudinal-(A, arrows) ...
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... enlargement of the lateral, third, and fourth ventricles observed in our MR images ( Fig. 2A) and histological examination (Fig. 3) are commonly observed in most neurodegenerative disorders and are caused by brain parenchymal shrinkage. Significant ventricular enlargement has been clinically associated with AD as a strong biomarker of disease progression [35,38,39], due to AD subjects exhibiting significant ventricle enlargement progress much faster than normal ...
Citations
... We confirmed, herein, cognitive impairments in this model at 2 and 4 weeks post-STZ using object recognition tests to assess short and long-term memory, which are dependent on the integrity of the hippocampus [22]. In rodents and non-human primates, the STZ model is reported to induce neurochemical changes similar to those observed in AD [28], as well as a reduction in the in vivo uptake of 18 F-deoxyglucose [29], strengthening the idea that hypometabolism of glucose is an early marker of AD. Accordingly, using this model, in rats, we previously described an increase in insulin receptor substrate 1 resistance, a reduction in protein NAGylation [9] and a reduction in deoxyglucose uptake in ex vivo hippocampal preparations (see Fig. 3). ...
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.
... Besides rats and mice, monkeys have also received icv-STZ injections in an attempt to establish a non-transgenic primate alternative model of AD (Yeo et al., 2015). After icv administration of four dosages of STZ (2 mg/kg), cynomolgus monkeys (Macaca fascicularis) presented progressive brain ventricular dilation and cerebral atrophy with severe cell loss, abnormal tau hyperphosphorylation in both temporal cortex and hippocampus, and neuroinflammation (Yeo et al., 2015). ...
... Besides rats and mice, monkeys have also received icv-STZ injections in an attempt to establish a non-transgenic primate alternative model of AD (Yeo et al., 2015). After icv administration of four dosages of STZ (2 mg/kg), cynomolgus monkeys (Macaca fascicularis) presented progressive brain ventricular dilation and cerebral atrophy with severe cell loss, abnormal tau hyperphosphorylation in both temporal cortex and hippocampus, and neuroinflammation (Yeo et al., 2015). Aβ deposition was observed in the cerebral cortex of these monkeys, however, the authors did not identify any Aβ pathology in their hippocampus (Yeo et al., 2015). ...
... After icv administration of four dosages of STZ (2 mg/kg), cynomolgus monkeys (Macaca fascicularis) presented progressive brain ventricular dilation and cerebral atrophy with severe cell loss, abnormal tau hyperphosphorylation in both temporal cortex and hippocampus, and neuroinflammation (Yeo et al., 2015). Aβ deposition was observed in the cerebral cortex of these monkeys, however, the authors did not identify any Aβ pathology in their hippocampus (Yeo et al., 2015). Therefore, although there are some contradictory results regarding Aβ pathology is this sporadic AD model, the data presented in the literature seem coherent and indicate that icv-STZ injections are able to induce AD-like behavioral and molecular alterations. ...
Since glucose reuptake by neurons is mostly independent of insulin, it has been an intriguing question whether insulin has or not any roles in the brain. Consequently, the identification of insulin receptors in the central nervous system has fueled investigations of insulin functions in the brain. It is also already known that insulin can influence glucose reuptake by neurons, mostly during activities that have the highest energy demand. The identification of high density of insulin receptors in the hippocampus also suggests that insulin may present important roles related to memory. In this context, studies have reported worse performance in cognitive tests among diabetic patients. In addition, alterations in the regulation of central insulin pathways have been observed in the brains of Alzheimer's disease (AD) patients. In fact, some authors have proposed AD as a third type of diabetes and recently, our group proposed insulin resistance as a common link between different AD hypotheses. Therefore, in the present narrative review, we intend to revise and gather the evidence of disturbed insulin signaling in experimental animal models of AD.
... Despite the proven beneficial effect in rat and murine models with different insults [5,7,23,24] and lack of toxicity in Sprague Dawley rats [2], 4R safety was never studied in a species close to humans. Nonhuman primates (NHPs) share structural and functional similarities to the human brain, liver, and kidney [25][26][27] and are the most important model in various biomedical research fields, including neurodegenerative disorders [28,29]. This study aimed to determine the safety of a repeated i.v. ...
The tobacco cembranoid (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is known to induce neuroprotection against brain ischemia, systemic inflammation, Parkinson's disease, and organophosphate toxicity in rodents. Studies examining the compound's safety in male and female Sprague Dawley rats demonstrated no significant side effects after a single injection of 4R at various concentrations (6, 24, or 98 mg/kg). To evaluate the neurotherapeutic feasibility of 4R for clinical trials, we have assessed the safety of this compound in nonhuman primates. We investigated whether 4R induces toxicity in male Macaca mulatta when administered for 11 consecutive days via intravenous injection at a dose of 1.4 mg/kg. Electroencephalogram, somatosensory evoked potential, and transcranial motor evoked potentials were measured at days 0, 4, 8, and 12 and remained unaffected during the experimental study. Spontaneous behavior was not affected between the groups. Small histopathological changes in the organs were observed in some animals, both treated and non-treated; thus, these changes cannot be attributed to 4R. Minor hematological and blood composition variations with no clinical significance were detected in the experimental animals. In conclusion, our data support previous findings that 4R is a non-toxic compound that proved safe in nonhuman primates during the given period and dose.
... Three-dimensional (3D) sagittal T1-weighted images were acquired using the turbo field echo sequence with the following settings: TR/TE=14/6.8 ms, 128×128 field-of-view (FOV), matrix size 256×256, voxel size 0.5×0.5×0.5, and number of slices=150. The details of the MRI protocols were the same as those described in a previous report [25]. ...
... To apply the XperCT-guided ICM administration system, we selected STZ, which is known to trigger AD pathology in cynomolgus monkeys [25][26][27]. We injected aCSF (vehicle group; n=2) and STZ (2 mg/kg; STZ group; n=2) using XperCT-guided ICM at weeks 1, 2, 3, and 4 ( Table 1). ...
... Earlier studies have confirmed that accurate and reproducible access to the CSF using ICM injection ensures the diffusion of the drug into the parenchyma and is similar to the diffusion observed after ICV injection [46,47]. Therefore, we previously developed a clinically relevant STZ-administered AD model using ICM injection in monkeys and rats, which is characterized by cerebral damage, disintegration of the neurovascular unit, neuroinflammation, amyloid deposition, neuronal loss, and tau phosphorylation [25,27,48]. However, there are some technical challenges and limitations to constructing stable and reproducible AD NHP-based models, including high costs and skilled technical infrastructure of XperCT. ...
Till date, researchers have been developing animal models of Alzheimer's disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM. Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.
... All NHP experiments in this study were approved by the Korea Research Institute of Bioscience and Biotechnology Institutional Animal Care and Use Committee (Approval No. KRIBB-AEC-20290) and have been reported in compliance with the ARRIVE guidelines [21,22]. As previously reported [17,[23][24][25][26][27], all experimental monkeys were used that were maintained at the National Primate Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB). To prevent potential damage to other monkeys via the metabolites of MPTP, monkeys were averted from having physical contact but were allowed visual and auditory contact with their neighbors. ...
The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson’s disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.
... STZ at a subdiabetogenic dose of 3mg/kg in two divided doses viz., i.c.v. route produces memory dysfunction like AD [7][8][9] . STZ infusion leads to enhanced oxidative and nitrosative stress, brain atrophy, neuronal loss, neuroinflammation, along with A β accumulation and tau hyperphosphorylation. Impaired synthesis of acetyl coenzyme A, ATP and creatine phosphate were observed. ...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised pathologically by the presence of extracellular amyloid plaques and the intracellular neurofibrillary tangles, along with inflammation, and a compromised antioxidant system. Significant insights into the neurobiology to better understand the pathophysiology of AD and to evaluate the possibility of cutting-edge therapy strategies, can be obtained through the selection of a well-designed experimental animal model. From the transgenic to chemical/drug-induced models, none of them represents the complete picture of Alzheimer pathology and incidence of cognitive dysfunction. Researchers did not explain why one model was preferred over another, did not consider how the pathological phenomena were formed (spontaneously, experimentally, or by genetic manipulation), and did not address the traits of the species that affect the results. There is a lack of concordance between preclinical models and clinical trials that could be due to variety of reasons such as incomplete models, choice of animal species, lack of variability, and the validity of the models. To provide greater translation of preclinical AD studies to clinical trials proper designing of the model is essential. This review provides a brief recap ranging from animal doses to their induction mechanism and common limitations of the chemical-induced AD models.
• Animal models may fail to replicate the exact pathology of the disease
• Validity of the model is essential for proper translation of pathology from animal models to human disease
• Appropriate induction doses need to be administered.
... In animal studies, we often use intracerebroventricular injection of streptozotocin (STZ) at a sub-diabetic dose to induce sporadic AD as well as behavioral, neurochemical, and histological hallmarks similar to those found in humans with AD (Lee et al. 2014;Grieb 2016). STZ administration leads to the impairment of various cognitive functions, cholinergic decline, glial activation, neural loss, amyloid angiopathy, and other AD-like changes in the brain regions (Yeo et al. 2015;Mehla et al. 2013). It has been revealed that i.c.v. ...
Numerous studies have shown the deleterious effects of sleep deprivation (SD) on memory. However, SD in various durations may induce different effects. Studies have reported that short-term or acute SD can improve cognitive functions. In addition, streptozotocin (STZ) significantly impairs learning and memory, and induces inflammation and oxidative stress. In this study, we aimed to investigate the effect of two types of SD (short term: 6 h; long term: 24 h) on STZ-induced spatial memory impairment in rats, with respect to the serum level of catalase (CAT), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β). Morris water maze apparatus was used to assess spatial memory performance and STZ was injected i.c.v., twice, and at the dose of 3 mg/kg, at an interval of 48 h. The results showed that only 24 h SD impaired spatial learning and memory in rats. In addition, 24 h SD attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum. STZ impaired spatial learning and memory, and attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum of rats. Furthermore, 6 h SD slightly and partially improved spatial memory and significantly improved anti-oxidant activity in rats, with no effect on STZ-induced inflammation. We suggest that STZ has more important mechanisms that are involved in its memory impairment effect, and maybe, STZ-induced inflammation has a more important role. We also suggest more detailed studies to investigate the potential therapeutic effect of SD (in different durations) on memory function, oxidative stress, and inflammation.
... Intracerebroventricular (icv) injection of streptozotocin (STZ), in subdiabetogenic dose, is an appropriate rat model that resembles the multifactorial pathogenesis and symptoms of sporadic AD (Correia et al. 2011;Grieb 2016). It caused neuronal loss and memory impairments through oxidative stress, neuroinflammation, cholinergic deficits, tau hyperphosphorylation, and increased amyloid-beta deposition (Lee et al. 2014;Yeo et al. 2015;Ravelli et al. 2017). ...
Alzheimer’s disease (AD) is the most common neurodegenerative disorder among the elderly. In the light of increasing AD prevalence and lack of effective treatment, new strategies to prevent or reverse this condition are needed. Levetiracetam (LEV) is a newer antiepileptic drug that is commonly used to treat certain types of seizures. Researches indicated that LEV has several other pharmacological activities, including improvement of cognitive function. In this study, the recovery effects of chronic (28 days) administration of LEV (50, 100, and 150 mg/kg, ip) on cognitive deficits caused by the intracerebroventricular (icv) injection of streptozotocin (STZ), as a model for sporadic AD, were evaluated in rats. We also considered the protective effects of LEV against hippocampal cell loss, oxidative damage, acetylcholinesterase (AChE) activity, neuroinflammation, and tauopathy caused by STZ. LEV (100 and 150 mg/kg) significantly attenuated the STZ-induced learning and memory impairments in the passive avoidance and Morris water maze (MWM) tasks. In addition, LEV suppressed STZ-induced hippocampal neuronal loss, while restored alterations in the redox status (lipid peroxides and glutathione), AChE activity, proinflammatory cytokines (IL-1β, IL-6, TNF-α), and hyperphosphorylation of tau linked to STZ administration. In conclusion, our study demonstrated that LEV alleviated hippocampal cell death and memory deficits in STZ-AD rats, through mitigating oxidative damage, suppression of proinflammatory cytokines expression, and inhibition of abnormal tau hyperphosphorylation.
... This animal experiment was approved by the Korea Research Institute of Bioscience and Biotechnology Institutional Animal Care and Use Committee (Approval No. KRIBB-AEC-16068) [9,[16][17][18][19][20][21]. MPTP treated NHP models are used to reproduce essential behavior PD signs, since they show a higher similarity to human patients with PD than other animals [22][23][24][25]. ...
Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.
... We used three adult (12-year-old) female cynomolgus macaques (Macaca fascicularis), which were obtained from Suzhou Xishan Zhongke Laboratory Animal Co. (Suzhou, China) and maintained in individual indoor cages at the National Primate Research Center (NPRC) in the Korea Research Institute of Bioscience and Biotechnology (KRIBB), as described previously [21,22]. Animal was fed commercial monkey chow (Harlan, USA), supplemented with various fruits and water ad libitum. ...
Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.
