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Journal : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment Ronny T Wirasto; Irwan Supriyanto; Arif Prassetyo; Nunu N Madjid; Susini R Sari; Baiq R Rhadianaa; Heru Yulianto; Nur Arfian; Nyoman Kertia
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 3 (2016)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (16.783 KB) | DOI: 10.19106/JMedSci004803201604

Abstract

ABSTRACTVascular cognitive impairment (VCI) is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651). The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively). In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction.
Prolonged Kidney Ischemia-Reperfusion Injury Associates with Inflammation, Vascular Remodelling, and Myofibroblast Formation Nur Arfian*; Hilma Kholida Ats-tsani; Pratiwi Indah Sayekti; Dwina Agrila Lakabela; Amelia Amelia; Toni Febriyanto; Hana Rutyana Putri Antonio; Dian Prasetyo Wibisono; Dwi Cahyani Ratna Sari
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 1 (2018)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1436.153 KB) | DOI: 10.19106/JMedSci005001201801

Abstract

Prolonged kidney ischemia-reperfusion injury (IRI) is the important risk factor for leading to chronic kidney disease (CKD). Persistent hypoxia and inflammation are considered as the main pathogenesis of chronic injury, followed by myofibroblast expansion and fibrosis process. Tubular injury, cell proliferation, and vasoconstriction, as acute compensatory responses, are restored in chronic phase. The aim of the study was to investigate the relation between inflammation, vascular remodeling, and myofibroblast formation as response to ischemia injury after prolonged kidney ischemia-reperfusion (I/R). Fifteen male Swiss mice aged 3-4 months were used as kidney I/R injury model after bilateral pedicle renal clamping. Rats were divided into 3 groups with five rats in each group i.e. control group (sham operation/SO), acute I/R model (IR1), and chronic I/R model (IR12). PAS staining was used for scoring tubular injury. Fibrosis was assessed using sirius red and a-SMA immunostaining for myofibroblast expansion. PCNA and CD68 immunostaining were used for identifying cell proliferation and macrophage infiltration. RT-PCR was conducted for assessing MCP-1, HIF-1a, and ppET-1 expression, which were quantified using ImageJ software. Data were analyzed using one way ANOVA and Kruskal-Wallis test with significance level of p<0.05. Significantly increase of tubular injury score (p<0.001) and PCNA positive cell (p<0.001) in IR1 group compared to SO were observed, otherwise HIF-1a of IR12 enhanced (p<0.05). Macrophage cell count (p<0.01) and MCP-1 expression (p<0.05), were significantly increase in IR1 and IR12 injury, compared to SO. Wall thickness of arteries was significantly increase (p<0.05) as well as decrease of vascular lumen area (p<0.05), followed by enhancement of ppET-1 expression (p<0.01) in IR1 group and restored significantly (p<0.05) in IR12 group. Fibrosis fraction-area and myofibroblast expansion were significantly increase gradually from IR1 to IR12 injury (p<0.01). In conclusion, prolonged kidney I/R injury induces the sustainability of hypoxia and inflammatory response, which promotes myofibroblast formation, and decrease the response of vascular remodelling. 
Ethanolic extract of the Centella asiatica (L.) Urb. leaf decreases cerebellar brain-derived neurotrophic factor (BDNF) levels in rats after chronic stress Dwi Cahyani Ratna Sari; Desby Juananda; Mawaddah Ar-Rochmah; Muhammad Mansyur Romi; Nur Arfian
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 2 (2018)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (770.994 KB) | DOI: 10.19106/JMedSci005002201801

Abstract

Chronic stress produces glucocorticoid-induced neurotoxicity that may lead to alterations of the brain-derived neurotrophic factor (BDNF) concentration in the brain. Cerebellum is known to be severely affected by glucocorticoids-associated oxidative damage. Centella asiatica (L.) Urb. may protect neurons from oxidative damage. This study aimed to investigate the effect of ethanolic extract of C. asiatica (L.) Urb. leaf on the rat cerebellar BDNF levels following stress. Twenty young-adult male Sprague Dawley rats were randomly assigned into four experimental groups. The stress control group received aquadest, and the other groups were treated with different doses of the C. asiatica (L.) Urb. extract i.e 150 (CeA150), 300 (CeA300) and 600 (CeA600) mg/kg body weight/day orally, respectively and followed by chronic footshock stress for 28 days. Upon completion of the experimental period, all animals were sacrificed and the cerebellar was isolated. The BDNF levels from the cerebellar tissue lysate was measured using ELISA. The mean BDNF levels of the cerebellar tissue in the stress control, CeA150, CeA300 and CeA600 groups were 1217.10±301.40; 771.46±241.45; 757.05±268.29; and 627.00±246.02 pg/mL, respectively. Post-hoc analysis showed a significant difference between the control and treatment groups (p< 0.05). In conclusion, the ethanolic extracts of the C. asiatica (L.) Urb. leaf decrease the cerebellar BDNF levels in rats after chronic stress.
The effects of furosemide on kidney damage in acute kidney injury rat models Afifah Afifah; . Ngatidjan; Nur Arfian
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 3 (2018)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (715.083 KB) | DOI: 10.19106/JMedScie/005003201801

Abstract

The most frequent cause of acute kidney injury (AKI) is ischemia reperfusion injuriesthat causes inflammation. Furosemide is still used in AKI’s therapy. The advantages anddisadvantages of furosemide in AKI remain controversial. The aim of the study was toinvestigate the effect of furosemide on kidney damage in AKI rat models. Twenty-fivemale (2-3 months old) Sprague-Dawley rats were divided into 5 groups; sham operation(SO, n=5), ischemic-reperfusion (IR, n=5), IR+furosemide 3.6 mg/kgBW (IR+F1,n=5), IR+furosemide 7.2 mg/kgBW (IR+F2, n=5), and IR+furosemide 14.4 mg/kgBW(IR+F3, n=5). Abdominal surgery was performed under ketamine anesthesia to produceischemic reperfusion (IR) by mean of renal artery clamping for 45 min. Urine output,serum creatinine level, tubular injury score, and TLR4 gene expression were examinedto investigate kidney damage. Periodic acid-schiff (PAS) staining was measured toexamine kidney tubular injury. Data were analyzed using One-Way ANOVA and Kruskal-Wallis test with significance level of p<0.05. AKI rat models which were given 3.6 and7.2 mg/kgBW of furosemide (0.014±0.001 mL/min; and 0.012±0.007) showed higher(p>0.05) creatinine clearance compared to IR (0.009±0.003) while administration of 14.4mg/kgBW furosemide (0.009±0.004) denoted equal creatinine clearance to IR (p>0,05).Kidney tubular injury score of 3.6 mg/kgBW furosemide (2.89±0.13) was lower (p>0.05)than IR (3.26±0.19) whereas 7.2 mg/kgBW and 14.4 mg/kgBW furosemide (3.55±0.26;3.83±0.19) were higher (p<0.05) than IR. Administration of 3.6 mg/kgBW furosemide(0.99±0.08) indicated lower (p<0.05) TLR4 gene expression than IR (1.20±0.08) whilst7.2 mg/kgBW furosemide (1.23±0.13) was not-significantly higher (p>0.05) and 14.4 mg/kgBW furosemide (1.63±0.12) was significantly higher (p<0.05) than IR. In conclusion,administration of 3.6 mg/kgBW furosemide reduces kidney damage in AKI rat modelswhile higher dosages (7.2 mg/kgBW and 14.4 mg/kgBW) increase kidney damage.
Increased blood-brain barrier permeability correlate with microglial activation at hippocampal CA1 region in acute and chronic bilateral common carotid artery ligation in rats Dian Prasetyo Wibisono; Nur Arfian; Handoyo Pramusinto; Fauziyatul Munawaroh; Yeshua Putra Krisnugraha; Daniel Agriva Tamba; Dwi Cahyani Ratna Sari
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 54, No 2 (2022)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.19106/JMedSci005402202201

Abstract

Inflammatory processes might play a key role in the pathogenesis of post-stroke epilepsy. The activation of microglia and release of vascular cell adhesion molecule-1 (VCAM1) might induce blood-brain barrier (BBB) disintegration. However, the influence of such pathomechanisms in the generation of post-stroke epilepsy is still not clear. We investigated whether cerebral ischemia exerts effects on inflammation in the hippocampus by measuring the hippocampal injury score, expression of a microglial marker, and expression of VCAM1 in rats. A total of 24 Sprague Dawley rats were randomized into four groups with 6 rats in eachgroup i.e. sham operation (SO) as control, carotid ligation 1 (GCL1) as an acute model, carotid ligation 3 (GCL3) as a subacute model, and carotid ligation 7 (GCL7) as a chronic model. Immunostaining for microglia marker (CD68) was measured in rat brain tissue sections. The VCAM1 expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Cerebral ischemia increased the amount of microglial immunostaining and expression of VCAM1. The hippocampal injury score and microglial immunopositivity were significantly correlated with the duration of brain ischemia. We conclude that cerebral ischemia is correlated with neuroinflammatory reaction and disturbance of BBB permeability, and the correlation of those molecular impairments with the generation of post-stroke epilepsy remains to be elucidated.