Lasting Pure-Motor Deficits after Focal Posterior Internal Capsule White-Matter Infarcts in Rats

Blasi, Francesco; Whalen, Michael J.; Ayata, Cenk

doi:10.1038/jcbfm.2015.7

Cited by 20 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thalamic infarcts were produced by injection of the potent vasoconstrictor endothelin-1 causing transient ischemia. 11,12 Briefly, isoflurane anesthetized rats (4% induction, 2.5% to 2% maintenance, in 70%N 2 O/30%O 2 ) were placed on a stereotactic frame (Stoelting, Wood Dale, IL, USA), and the body temperature was maintained at 37°C. A burr hole was drilled under saline cooling, and 1 μL of endothelin-1 (0.3 mg/mL, American Peptide, Sunnyvale, CA, USA; n = 12) or vehicle (sterile saline; n = 12) was injected (0.1 μL/min) using a 10 μL syringe (Hamilton, Reno, NV, USA; 33 gauge beveled needle, outer diameter: 0.21 mm) via a micropump (Stoelting).…”

Section: Methodsmentioning

confidence: 99%

Late-Onset Thermal Hypersensitivity after Focal Ischemic Thalamic Infarcts as a Model for Central Post-Stroke Pain in Rats

Blasi

Herisson

Wang

et al. 2015

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

Central post-stroke pain (CPSP) is a neuropathic pain syndrome that often develops in a delayed manner after thalamic stroke. Here, we describe a new model of CPSP by stereotaxic thalamic injection of endothelin-1. Stroke rats (n = 12), but not saline-injected controls (n = 12), developed a progressive, contralateral cutaneous thermal hyperalgesia over 4 weeks, without motor deficits. Lesions were highly focal and mainly affected the ventral posterior thalamic complex. Tchis model reproduces the infarct location and delayed hypersensitivity typical of CPSP, and may be useful to investigate its pathophysiology and test therapies targeting recovery and pain after thalamic stroke. INTRODUCTIONCentral post-stroke pain (CPSP) is a neuropathic pain syndrome characterized by constant or recurrent pain after central nervous system injury. 1 Central post-stroke pain can be triggered by either an ischemic or hemorrhagic infarct at any level of the spinothalamic pathway and its cortical projections often involving the thalamus. 2 Central post-stroke pain is frequently overlooked, and can be misdiagnosed as musculoskeletal pain resulting from paresis and/or muscle tone abnormalities. 3 Epidemiological data are scarce, probably because of the difficulty in interpreting the clinical signs and the variable symptom onset. Thus, CPSP is often perceived as a rare event. 4 However, the true incidence in stroke patients is as high as 8% to 11%. 5 The pathophysiology of CPSP is still poorly understood, and therapeutic options are limited in part owing to a lack of clinically relevant animal models. 6 For example, experimental CPSP models involving thalamic hemorrhage all show acute onset of the pain symptoms, 7,8 in contrast to the delayed onset of CPSP several weeks later in patients. 4 To address these shortcomings, we aimed to develop a new experimental model that better mimics the lateonset hypersensitivity seen in CPSP patients. Recently, two clinical reports linked CPSP to more posterior, inferior, and lateral thalamic infarcts, clustering at the ventral posterior thalamic nuclei. 9,10 These relay nuclei receive inputs from medial lemniscus, spinothalamic, and trigeminothalamic tracts, and project to the somatosensory cortex where noxious and non-painful, thermal, and mechanical stimuli are processed. We, therefore, targeted the ventral posterior thalamic complex by using stereotaxic microinjections of endothelin-1 to create highly focal ischemic lesions in rats.

show abstract

Section: Methodsmentioning

confidence: 99%

Late-Onset Thermal Hypersensitivity after Focal Ischemic Thalamic Infarcts as a Model for Central Post-Stroke Pain in Rats

Blasi

Herisson

Wang

et al. 2015

J Cereb Blood Flow Metab

Self Cite

View full text Add to dashboard Cite

show abstract

“…The colours of the corticospinal neurons correspond to the body parts that they control as in the motor cortical regions in part a . The rat coronal sections show the locations of ischaemic infarcts that have been used to model post-stroke upper-extremity impairments; these infarcts are located in the forelimb region of the primary motor cortex 69,73 (M1; which is supplied by the distal middle cerebral artery) and in the posterior limb of internal capsule 77,190 (which is supplied by the anterior choroidal artery). The dashed lines indicate the disconnection of descending cortical projections.…”

Section: Figure 1 |mentioning

confidence: 99%

Motor compensation and its effects on neural reorganization after stroke

2017

View full text Add to dashboard Cite

Stroke instigates a dynamic process of repair and remodelling of remaining neural circuits, and this process is shaped by behavioural experiences. The onset of motor disability simultaneously creates a powerful incentive to develop new, compensatory ways of performing daily activities. Compensatory movement strategies that are developed in response to motor impairments can be a dominant force in shaping post-stroke neural remodelling responses and can have mixed effects on functional outcome. The possibility of selectively harnessing the effects of compensatory behaviour on neural reorganization is still an insufficiently explored route for optimizing functional outcome after stroke.

show abstract

“…ET-1 has recently been used to induce focal ischemia leading to impaired executive memory function and to impaired pure-motor and sensorimotor behaviors that are dependent on the specific area of ischemic insult in rodents7891011. There have been a few non-human primate studies utilizing ET-1 induced cerebral ischemia models developed in marmoset monkeys1213.…”

mentioning

confidence: 99%

A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

Dai

Huang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3–8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke.

show abstract

Lasting Pure-Motor Deficits after Focal Posterior Internal Capsule White-Matter Infarcts in Rats

Cited by 20 publications

References 40 publications

Late-Onset Thermal Hypersensitivity after Focal Ischemic Thalamic Infarcts as a Model for Central Post-Stroke Pain in Rats

Late-Onset Thermal Hypersensitivity after Focal Ischemic Thalamic Infarcts as a Model for Central Post-Stroke Pain in Rats

Motor compensation and its effects on neural reorganization after stroke

A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

Contact Info

Product

Resources

About