Academic literature on the topic 'Neuroscore'

The goal of the present study was to test the impact of administration time of the angiotensin II type 1–receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 ± 8), infarct size in candesartan-treated groups was smaller (59 ± 5, 68 ± 10, 28 ± 3, and 15 ± 3, respectively; P < 0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 ± 0.18, 1.80 ± 0.13), other treatment regimens resulted in improved neuroscores (1.33 ± 0.16, 1.11 ± 0.11, 0.73 ± 0.15; P < 0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 ± 0.09 mL · g−1 ·· min−1 and 44% ± 7% of baseline compared with 0.49 ± 0.06 mL · g−1 ·· min−1 and 37% ± 6%, microspheres and laser-Doppler flowmetry; P < 0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.

Cerebellar haemorrhage accounts for 5–10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

Glial scarring is traditionally thought to be detrimental after stroke. But emerging studies now suggest that reactive astrocytes may also contribute to neurovascular remodeling. Here, we assessed the effects and mechanisms of metabolic inhibition of reactive astrocytes in a mouse model of stroke recovery. Five days after stroke onset, astrocytes were metabolically inhibited with fluorocitrate (FC, 1 nmol). Markers of reactive astrocytes (glial fibrillary acidic protein (GFAP), HMGB1), markers of neurovascular remodeling (CD31, synaptophysin, PSD95), and behavioral outcomes (neuroscore, rotarod latency) were quantified from 1 to 14 days. As expected, focal cerebral ischemia induced significant neurological deficits in mice. But over the course of 14 days after stroke onset, a steady improvement in neuroscore and rotarod latencies were observed as the mice spontaneously recovered. Reactive astrocytes coexpressing GFAP and HMGB1 increased in peri-infarct cortex from 1 to 14 days after cerebral ischemia in parallel with an increase in the neurovascular remodeling markers CD31, synaptophysin, and PSD95. Compared with stroke-only controls, FC-treated mice demonstrated a significant decrease in HMGB1-positive reactive astrocytes and neurovascular remodeling, as well as a corresponding worsening of behavioral recovery. Our results suggest that reactive astrocytes in peri-infarct cortex may promote neurovascular remodeling, and these glial responses may aid functional recovery after stroke.

In the traumatic brain injury (TBI) the initial impact causes both primary injury, and launches secondary injury cascades. One consequence, and a factor that may contribute to these secondary changes and functional outcome, is altered hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after severe controlled cortical impact injury were characterized to assess their interrelations with motor function impairment. Magnetic resonance imaging (MRI) was performed 1, 2, 4 h, and 1, 2, 3, 4, 7, and 14 days after TBI to quantify CBV and water diffusion. Neuroscore test was conducted before, and 2, 7, and 14 days after the TBI. We found distinct temporal profile of CBV in the perilesional area, hippocampus, and in the primary lesion. In all regions, the first response was drop of CBV. Perifocal CBV was reduced for over 4 days thereafter gradually recovering. After the initial drop, the hippocampal CBV was increased for 2 weeks. Neuroscore demonstrated severely impaired motor functions 2 days after injury (33% decrease), which then slowly recovered in 2 weeks. This recovery parallelled the recovery of perifocal CBV. CBV MRI can detect cerebrovascular pathophysiology after TBI in the vulnerable perilesional area, which seems to potentially associate with time course of sensory-motor deficit.

Small retrospective studies have shown the benefit of endovascular treatment with intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) with/without IST (MT+/−IST) in cases of multifocal cerebral venous thrombosis (CVT). Our study compares the mortality, functional outcome and periprocedural complications among patients treated with MT +/– IST versus IST alone. We reviewed clinical and angiographic findings of 63 patients with CVT who received endovascular treatment at three tertiary care centers. Primary outcome variables were discharge mortality and neurological dysfunction, and intermediate (three months) and long-term (>six months) morbidity. The modified Rankin scale (mRS) was used to assess morbidity. mRS ≤1 was considered a good recovery. Neurological dysfunction was rated as neuroscore: 0, normal; 1, mild (ambulatory, communicative); 2, moderate (non-ambulatory, communicative); and 3, severe (non-ambulatory, non-communicative/comatose). In patients who received IST alone, presenting neurological deficits were comparatively minor (p<0.001). When the two groups were adjusted for admission neuroscore, there was no statistical significance between discharge mortality [7(21%) versus 4(14%), p=0.228], neurological dysfunction (p=0.442), intermediate (p=0.336) and long-term morbidity (p=0.988). Patients who received MT +/- IST had a higher percentage of periprocedural complications without reaching statistical significance. Compared to IST, MT was performed in severe cases with extensive sinus involvement. When adjusted for admission neurological dysfunction, both groups had similar mortality and discharge neurological dysfunction and similar intermediate and long-term morbidity.

Abstract Purpose A substantial number of ischaemic stroke patients who receive reperfusion therapy in the acute phase do not ever fully recover. This reveals the urgent need to develop new adjunctive neuroprotective treatment strategies alongside reperfusion therapy. Previous experimental studies demonstrated the potential of glucagon-like peptide-1 (GLP-1) to reduce acute ischaemic damage in the brain. Here, we examined the neuroprotective effects of two GLP-1 analogues, liraglutide and semaglutide. Methods A non-diabetic rat model of acute ischaemic stroke involved 90, 120 or 180 min of middle cerebral artery occlusion (MCAO). Liraglutide or semaglutide was administered either i.v. at the onset of reperfusion or s.c. 5 min before the onset of reperfusion. Infarct size and functional status were evaluated after 24 h or 72 h of reperfusion. Results Liraglutide, administered as a bolus at the onset of reperfusion, reduced infarct size by up to 90% and improved neuroscore at 24 h in a dose-dependent manner, following 90-min, but not 120-min or 180-min ischaemia. Semaglutide and liraglutide administered s.c. reduced infarct size by 63% and 48%, respectively, and improved neuroscore at 72 h following 90-min MCAO. Neuroprotection by semaglutide was abolished by GLP1-R antagonist exendin(9-39). Conclusion Infarct-limiting and functional neuroprotective effects of liraglutide are dose-dependent. Neuroprotection by semaglutide is at least as strong as by liraglutide and is mediated by GLP-1Rs.

The authors evaluated the neurobehavioral and neuropathologic sequelae after traumatic brain injury (TBI) in transgenic (TG) mice expressing truncated high molecular weight neurofilament (NF) protein fused to beta-galactosidase (NFH-LacZ), which develop Lewy body-like NF-rich inclusions throughout the CNS. TG mice and their wild-type (WT) littermates were subjected to controlled cortical impact brain injury (TG, n=19; WT, n=17) or served as uninjured controls (TG, n =11; WT, n =11). During a 3-week period, mice were evaluated with an array of neuromotor function tests including neuroscore, beam balance, and both fast and slow acceleration rotarod. Brain-injured WT and TG mice showed significant motor dysfunction until 15 days and 21 days post-injury, respectively ( P < .025). Compared with brain-injured WT mice, brain-injured TG mice had significantly greater motor dysfunction as assessed by neuroscore ( P < .01) up to and including 15 days post-injury. Similarly, brain-injured TG mice performed significantly worse than brain-injured WT mice on slow acceleration rotarod at 2, 8, and 15 days post-injury ( P < .05), and beam balance over 2 weeks post-injury ( P < .01). Histopathologic analysis showed significantly greater tissue loss in the injured hemisphere in TG mice at 4 weeks post-injury ( P < .01). Together these data show that NFH-LacZ TG mice are more behaviorally and histologically vulnerable to TBI than WT mice, suggesting that the presence of NF-rich inclusions may exacerbate neuromotor dysfunction and cell death after TBI.

Object. Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI. Methods. Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood—brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury, observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein—2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of β-amyloid or tau were observed in any brain-injured animal. Conclusions. On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.

L’ictus rappresenta la seconda causa di morte a livello globale e la prima causa di disabilità negli anziani. A causa di alcuni limiti di impiego, le principali terapie disponibili, volte a ripristinare il flusso sanguigno attraverso fibrinolisi e/o trombectomia meccanica, possono essere usate solo nel 60% dei pazienti con eziologia ischemica. Per tale motivo, la ricerca preclinica cerca di identificare target terapeutici utili per definire nuovi trattamenti ed estendere l’accesso alle cure. Nessuna nuova strategia terapeutica identificata negli studi preclinici ha però confermato la sua efficacia nei trial clinici. I problemi di traslazionalità dipendono da alcuni limiti degli studi preclinici, come l’uso di un ridotto numero di animali, che non rappresentano le condizioni reali dei pazienti o la mancata replicazione dei risultati ottenuti dai singoli laboratori, introducendo così bias metodologici, tra cui la mancanza di protocolli armonizzati. Il presente studio origina dalla necessità di migliorare il valore traslazionale della ricerca preclinica nell’ictus ischemico attraverso la definizione di un multicentre preclinical randomised controlled trial (pRCT), il progetto TRICS, che ha l’obiettivo di valutare l’azione neuroprotettiva del remote ischemic conditioning (RIC) dopo l’evento ischemico. Perché il RIC raggiunga una neuroprotezione significativa, l’outcome primario è che induca un miglioramento dei deficit sensorimotori a 48 ore dall’evento ischemico, calcolati attraverso il De Simoni neuroscore. Lo score valuta i deficit generali, che indicano lo stato di salute dell’animale e i deficit focali selettivamente associati alle conseguenze neurologiche dell’ischemia. Per ridurre al minimo i bias tecnici, il nostro studio ha previsto una prima fase di armonizzazione della valutazione comportamentale tra i centri, mediante analisi della concordanza tra i rater che eseguivano la misura, definita come interrater agreement. Questo è stato calcolato come intraclass correlation coefficient, ICC=0, nessun accordo, a ICC=1, accordo perfetto. Ci siamo posti l’obiettivo di raggiungere un interrater agreement con un ICC≥ 0.60. Una buona concordanza tra i centri è infatti una condizione indispensabile per garantire che tutti applichino lo stesso metodo di valutazione, assicurando l’oggettività, la trasparenza e la riproducibilità dei risultati. Dopo un training sull’esecuzione del De Simoni neuroscore, ogni centro ha indotto l’ischemia cerebrale nell’animale mediante l’occlusione transiente dell’arteria cerebrale media (tMCAo). A 48 ore dall’operazione, tutti gli animali sono stati filmati durante l’esecuzione del test e i video sono stati inviati al centro coordinatore, che li ha randomizzati e inoltrati ai centri. Un rater per ogni centro ha eseguito in cieco il De Simoni neuroscore sui video e sulle valutazioni è stata eseguita l’analisi statistica. Il risultato ottenuto dall’interrater agreement è stato di ICC=0.50 (0.22-0.77) per i topi e ICC=0.49 (0.210.77) per i ratti; non siamo riusciti a raggiungere l’obiettivo prefissato. Questi risultati sono dipesi da alcuni errori nell’esecuzione del test e dall’attribuzione sbagliata dei punteggi. È stata organizzata una seconda fase di training per superare le differenze di valutazioni più evidenti e preparati nuovi animali ischemici con cui sostituire i video che presentavano errori. Il risultato ottenuto dall’interrater agreement del secondo trial è stato di ICC=0.64 (0.37 – 0.85) per i topi e ICC=0.69 (0.44 - 0.88) per i ratti, soddisfacendo quindi il criterio per iniziare la fase interventistica dello studio. La fase di armonizzazione rappresenta un nuovo ed originale approccio nella ricerca preclinica e dovrebbe rappresentare lo schema di lavoro di base per pianificare uno studio pRCT al fine di renderlo solido e predittivo.
In view of fostering transferability of pre-clinical data on the efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, we designed two multi-centre translational trials in mice and rats of both sexes. We defined to model ischaemic stroke by the transient occlusion of the middle cerebral artery (tMCAo). The improvement of sensorimotor deficits at 48h after tMCAo in RIC-treated animals was defined as the primary outcome. This work presents the harmonization phase relative to the evaluation of sensorimotor deficits by De Simoni neuroscore. Each centre performed different tMCAo durations - 30, 45, 60 min - allowing sufficient variability in the outcome. Animals were monitored post-surgery according to the ARRIVE and IMPROVE guidelines and data was registered into an electronic case report form on RedCap. All animals were video recorded during the neuroscore and the videos (n=11 per species) were distributed and evaluated blindly by raters at all centres. The interrater agreement of neuroscore was described using intraclass correlation coefficient (ICC), ranging between ICC=0 (equivalent to chance) and ICC=1 (perfect agreement), setting a target of ICC≥0.60 as satisfactory. We obtained moderate agreement for mice (ICC=0.50 [0.22-0.77]) and rats (ICC=0.49 [0.21-0.77]). Errors were identified in animal handling and test execution. We thus performed a second training followed by a new blind evaluation replacing the videos with poor experimental execution. The interrater agreement improved for mice (ICC=0.64 [0.37-0.85]) and rats (ICC=0.69 [0.44-0.88]). In conclusion, two dedicated training on the neuroscore allowed us to reach the agreement target for both species and thus next proceed with the interventional phase of the project.