Long-term survival and serial assessment of stroke damage and recovery – practical and methodological considerations.

Modo, Mike

doi:10.6030/1939-067x-2.2.52

Cited by 15 publications

(16 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MCA was occluded for 70 min prior to reperfusion by retracting the filament to the common carotid bifurcation. After recovery from anesthesia, animals were assessed for forelimb flexion and contralateral circling with daily post-operative care and neurological assessment until they recovered pre-operative weight [35,36]. …”

Section: Methodsmentioning

confidence: 99%

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

et al. 2016

Self Cite

View full text Add to dashboard Cite

Brain tissue loss following stroke is irreversible with current treatment modalities. The use of an acellular extracellular matrix (ECM), formulated to produce a hydrogel in situ within the cavity formed by a stroke, was investigated as a method to replace necrotic debris and promote the infiltration of host brain cells. Based on magnetic resonance imaging measurements of lesion location and volume, different concentrations of ECM (0, 1, 2, 3, 4, 8 mg/mL) were injected at a volume equal to that of the cavity (14 days post-stroke). Retention of ECM within the cavity occurred at concentrations >3 mg/mL. A significant cell infiltration into the ECM material in the lesion cavity occurred with an average of ~36,000 cells in the 8 mg/mL concentration within 24 h. An infiltration of cells with distances of >1500 μm into the ECM hydrogel was observed, but the majority of cells were at the tissue/hydrogel boundary. Cells were typically of a microglia, macrophage, or neural and oligodendrocyte progenitor phenotype. At the 8 mg/mL concentration ~60% of infiltrating cells were brain-derived phenotypes and 30% being infiltrating peripheral macrophages, polarizing toward an M2-like anti-inflammatory phenotype. These results suggest that an 8 mg/mL ECM concentration promotes a significant acute endogenous repair response that could potentially be exploited to treat stroke.

show abstract

Section: Methodsmentioning

confidence: 99%

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…The MCA was occluded for 70 minutes prior to reperfusion by retracting the filament to the common carotid bifurcation. After recovery from anesthesia, animals were assessed for forelimb flexion and contralateral circling with daily post-operative care and neurological assessment until they recovered pre-operative weight [37, 38]. Animals not exhibiting signs of MCA damage or who failed to recover weight were excluded at this stage (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

“…The bilateral asymmetry test probed tactile extinction as a measure of sensory neglect [28, 37, 38]. For this, two strips of equal size (6 cm long, 0.5-0.8 cm wide) were applied with equal pressure to the saphenous part of the forepaw.…”

Section: Methodsmentioning

confidence: 99%

“…The footfault test evaluated the animals’ ability to integrate motor responses by analyzing motor impairments of limb functioning and placing deficits during locomotion [28, 37, 38]. The rats were placed in the Motorater System (TSE GmbH) with horizontal bars to record the placements of both unaffected and affected forelimbs over 8 trials (>60 placements).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume

et al. 2017

Self Cite

View full text Add to dashboard Cite

Salvaging or functional replacement of damaged tissue caused by stroke in the brain remains a major therapeutic challenge. In situ gelation and retention of a hydrogel bioscaffold composed of 8 mg/mL extracellular matrix (ECM) can induce a robust invasion of cells within 24 hours and potentially promote a structural remodeling to replace lost tissue. Herein, we demonstrate a long-term retention of ECM hydrogel within the lesion cavity. A decrease of approximately 32% of ECM volume is observed over 12 weeks. Lesion volume, as measured by magnetic resonance imaging and histology, was reduced by 28%, but a battery of behavioral tests (bilateral asymmetry test; footfault; rotameter) did not reveal a therapeutic or detrimental effect of the hydrogel. Glial scarring and peri-infarct astrocytosis were equivalent between untreated and treated animals, potentially indicating that permeation into host tissue is required to exert therapeutic effects. These results reveal a marked difference of biodegradation of ECM hydrogel in the stroke-damaged brain compared to peripheral soft tissue repair. Further exploration of these structure-function relationships is required to achieve a structural remodeling of the implanted hydrogel, as seen in peripheral tissues, to replace lost tissue and promote behavioral recovery.

show abstract

“…For this, under isoflurane (4% induction, 1% maintenance in 30% O 2 ) anesthesia, a 5-0 silicon rubber-coated monofilament (503556PK10, Doccol, USA) was advanced to the ostium of the MCA in the circle of Willis and the MCA was occluded for 70 minutes prior to reperfusion. After recovery from anesthesia, animals were assessed for forelimb flexion and contralateral circling with daily post-operative care and neurological assessment until they recovered pre-operative weight [36, 37]. …”

Section: Methodsmentioning

confidence: 99%

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

et al. 2017

Self Cite

View full text Add to dashboard Cite

Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity. In vitro imaging indicated a robust concentration-dependent detection of the ECM precursor and hydrogel at 1.8 and 3.6 ppm, which broadly corresponded to chondroitin sulfate and fibronectin. This detection was robust to changes in pH and improved at 37 °C. In vivo implantation of ECM hydrogel into the stroke cavity in a rat model corresponded macroscopically to the distribution of biomaterial as indicated by histology, but mismatches were also evident. Indeed, CEST imaging detected an endogenous “increased deposition”. To account for this endogenous activity, pre-implantation images were subtracted from post-implantation images to yield a selective visualization of hydrogel distribution in the stroke cavity and its evolution over 7 days. The CEST detection of ECM returned to baseline within 3 days due to a decrease in fibronectin and chondroitin sulfate in the hydrogel. The distribution of ECM hydrogel within the stroke cavity is hence feasible in vivo, but further advances are required to warrant a selective long-term monitoring in the context of biodegradation.

show abstract

Long-term survival and serial assessment of stroke damage and recovery – practical and methodological considerations.

Cited by 15 publications

References 102 publications

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

Contact Info

Product

Resources

About