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"Tujuan: Menganalisis ekspresi gen manganese superoxide dismutase (MnSOD) pada jaringan jantung, otak dan darah tikus yang diinduksi hipoksia sistemik.Desain: penelitian eksperimental in vivo dengan menggunakan hewan coba.Metode: Sampe! penelitizm ini adalah 25 ekor tikus jantan strain Sprague Dawley (Rarms novergicus L), yang dibagi menjadi 5 kelompok: kelompok I tikus tanpa perlakuan hipoksia sebagai kontrol, kelompok II, III, IV dan V adalah kelompok tikus dengan perlakuan hipoksia 10% O2 selama 1, 7, 14 dan 21 hari. Setelah perlakuan tikus dimaiikan, kemudian darah, otak dan jantung tikus diambil untuk diperiksa tingkat ekspresi mRNA dengan menggunakan real time RT PCR dengan pewamaan SYBR green, serta diukur aktivitas spesifik MnSOD dengan menggunakan kit RanSOD® dengan ditambahkan NaCN untuk menghambat aktivitas CuZn SOD.Hasil: Pada hipoksia awa] (1 hari) ekspresi relatif mRNA MnSOD dan aktivitas spesifik MnSOD menunjukkan penurunan di darah dan jantung, sedangkan pada otak tidak te1jadi penurunan. Hal ini menunjukkan bahwa dalam keadaan hipoksia sistemik perlindungan antioksidan pada otak terjadi lebih awal dibandingkan jantung dan darah. Pada hipoksia awal di jantung dan darah, mulai terjadi peningkatan ROS sehingga aktivitas spesink MnSOD menurun, namun belum dapat menstimulasi peningkatan eksprsi mRNA-nya_ Pada hipoksia I-I4 hari baik ekspresi mRNA maupun aktivitas spesiiik MnSOD pada ketiga jaringan tersebut mengalami peningkatan sejalan dengan lamanya hipoksia. Pada hipoksia lanjut (21 hari) terjadi korelasi negatif antara ekspresi relatif mRNA dngan aktivitas spesiiik MnSOD di jantung dan darah. Hal ini mnmgkin disebabkan karena produksi ROS yang sangat masif, sehingga ekspresi MRNA terus ditingkatkan namun stres oksidatif belum dapat diatasi, sedangkan pada otak fenomena tersebut tidak terjadi. Hal ini diduga karena peningkatan ROS pada hipoksia lanjut masih dapat diatasi dengan aktivitas enzim MnSOD yang tersedia tanpa harus meningkatkan ekspresi mRNA-nya. Hasil ini menunjukkan bahwa otak cenderung lebih dilindungi dalam keadaan hipoksia sistemik dibandingkan janrung dan darah. Hasil analisis uji korelasi Pearson menunjukkan bahwa perubahan ekspresi relatif MRNA dan aktivitas spesifik MnSOD pada induksi hipoksia sistemik pada darah sejalan dengan perubahannya pada jantung dan otak.Kesimpulan: Setiap jaringan mempunyai pola ekspresi gen MnSOD dan aktivitas MnSOD yang berbeda-beda pada kondisi hipoksia. Terdapat perbedaan regulasi ekspresi gen MnSOD antara hipoksia sistemik awal dan lanjut. Pengukuran ekspresi MnSOD (mRNA dan aktivitas spesifik) pada darah dapat sekaligus menggambarkan ekspresi tersebut pada jantung dan otak.

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Background: The aim of this study is to determine the gene expression of manganese supenoxide dismutase (MnSOD) in rat?s heart, brain and blood induced by systemic hypoxia.

Design: This study is an in vivo experimental study.

Method: This study was conducted on 25 male Sprague Dawley rats (Rattus no1°e:~_gicn.s~ L) which were divided into 5 groups and subjected to systemic hypoxia by placing them in hypoxic chamber supplied by 10% O3 for O, l, 7. I4, 2.1 days. respectively. Rats were sacrified after treatment, and the blood. heart and brain were used for measurement of relative mRNA level ofMnSOD with real time RT PCR and measurement of spesitic activity of MnSOD enzyme using RanSOD® kit.

Result: Determination of gene expression of MnSOD (relative mRNA expression and specific activity) in rat blood and heart cells under early hypoxic induction (1 day) resulted in the lower levels compared to the level in control group. After l day of hypoxic induction the gene expression level was then increased and again decreased under very late hypoxic condition (21 days) compared to the control. This suggests that the blood and heart cells at early hypoxia have not enough time to provide more MnSOD enzyme through gene expression to eliminate the sudden accumulation of ROS. In contrast to the results in heart and blood cells. the gene expression of MnSOD in brain cells were demonstrated to be increased since early systemic hypoxia (day I) up to day l4_ and tends to decrease under late hypoxic condition (day 21) although the level still slightly higher compared to the level in control group. Under late hypoxic condition (21 days). the capacity of1VlnSOD to eliminate the accumulated ROS has been saturated as found in brain cells, or even reduced to the lower level than in normal condition as found in blood and heart cells. This study could demonstrate that brain cells have different pattern of gene expression of MnSOD compared to blood and heart cells during several time points of hypoxic induction, particularly at early stage. It should also be considered that the levels of gene expression of MnSOD in each tissue were distinct although measured under the same condition. Analysis of Pearson correlation test shows that pattern of gene expression ot`MnSOD in blood cells is appropriate with the pattern in heart and brain cells under hypoxic condition.

Conclusion: Every tissue has the different pattern of gene expression of MnSOD (relative mRNA expression and specific activity) under hypoxic condition There is different regulation of MnSOD gene expression at early and late hypoxia Analysis gene expression of MnSOD in blood cells could represent the analysis of gene expression of MnSOD in heart and brain cells under hypoxia condition."

"Otak merupakan organ yang memiliki kebutuhan oksigen dan glukosa tertinggi di tubuh. Rendahnya tekanan oksigen pada otak dapat memicu terjadinya kerusakan pada sel otak bahkan kematian sel. Hipoksia merupakan kondisi penurunan kadar oksigen pada organ, jaringan atau sel. Hipoksia yang diberikan pada kadar dan waktu tertentu dapat menimbulkan respons adaptasi tubuh sehingga kondisi hipoksia dapat ditanggulangi. Salah satu respons adaptasi yang dilakukan adalah autofagi. Autofagi adalah suatu proses degradasi dan daur ulang molekul sitoplasmik dan organel seperti mitokondria dengan bantuan lisosom yang berperan dalam menjaga homeostasis seluler. Penelitian ini dilakukan untuk mengetahui efek pemberian hipoksia hipobarik intermiten terhadap aktivitas autofagi sel melalui ekspresi protein LC3 dan mTOR pada jaringan otak tikus. Penelitian ini menggunakan sampel jaringan otak tikus jenis Sprague-Dawley. Tikus dibagi dalam lima kelompok, yaitu kelompok kontrol, kelompok hipoksia 1 kali (HHI 1), HHI 2, HHI 3 dan HHI 4. Setiap kelompok hipoksia akan dimasukan dalam hypobaric chamber dan dibawa sampai ketinggian 25.000 kaki selama 5 menit. Tikus kemudian dikorbankan dan dilakukan pengukuran ekspresi protein LC3 dan mTOR menggunakan metode ELISA. Ekspresi protein LC3 juga dianalisis dengan IHK. Hasil menunjukkan bahwa pemberian perlakuan hipoksia hipobarik intermiten mampu meningkatkan ekspresi protein LC3 dan mempertahankan ekspresi mTOR. Hasil pulasan IHK menunjukkan ekspresi protein LC3 lebih tinggi pada bagian cerebellum otak dibandingkan dengan bagian cerebrum pada setiap kelompok.

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The brain is an organ with the highest demand for oxygen and glucose in the body. Insufficient oxygen pressure in the brain can lead to damage to brain cells and even cell death. Hypoxia is a condition characterized by a decrease in the oxygen levels in organs, tissues, or cells. Hypoxia, when applied at specific levels and durations, can induce adaptive responses in the body, allowing it to cope with the hypoxic conditions. One such adaptive response is autophagy. Autophagy is a cellular process involving the degradation and recycling of cytoplasmic molecules and organelles, including mitochondria, facilitated by lysosomes. This process plays a crucial role in maintaining cellular homeostasis. This study aimed to investigate the effects of intermittent hypobaric hypoxia on autophagic activity in brain cells by assessing the expression of proteins LC3 and mTOR during hypoxic conditions. The experimental subjects were Sprague-Dawley rats, and they were divided into five groups: a control group, and four groups subjected to intermittent hypobaric hypoxia (IHH) for varying durations (IHH1, IHH2, IHH3, and IHH4). Each IHH group was exposed to a hypobaric chamber at an altitude of 25,000 feet for 5 minutes. Subsequently, the rats were sacrificed, and the expression of LC3 and mTOR proteins was measured using ELISA. The LC3 protein expression was also analyzed through immunohistochemistry (IHC). The results showed that intermittent hypobaric hypoxia treatment increased the expression of LC3 protein and maintained mTOR expression. Additionally, IHC feedback indicated higher LC3 protein expression in the cerebellum region compared to the cerebrum in each experimental group."

""Summarizing the evidence and highlighting research from the past 20 years, the authors discuss lateralization from four perspectives - function, evolution, development, and causation - covering a wide range of animals including humans. The evolution of lateralization is traced from our earlier ancestors, through fish and reptiles to birds and mammals. The benefits of having a divided brain are discussed, as well as the influence of experience on its development. A final chapter discusses outstanding problems and areas for further investigation.""

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Latar Belakang

Brain Arteriovenous Malformation (BAVM) merupakan salah satu anomali vaskular pada otak yang dapat menyebabkan berbagai komplikasi. Baku emas untuk mendeteksi BAVM adalah dengan digital subtraction angiography (DSA), namun modalitas ini tidak tersedia secara luas di Indonesia. Penelitian ini disusun untuk memberikan gambaran profil karakteristik klinis dan temuan dari DSA, CT-Angiography (CTA), dan MR-Angiography (MRA) dalam sesuai penilaian Grade Spezler-Martin.

Metode

Data rekam medis dan hasil pencitraan kasus BAVM dengan DSA disertai atau tidak pemeriksaan MRA atau CTA didapat dari Departemen Bedah Saraf RSUPN Dr. Cipto Mangunkusumo (RSCM) pada periode 2018-2022. Kasus yang memenuhi kriteria inklusi dan eksklusi disertakan penelitian deskriptif obserasional ini.

Hasil

Terdapat total 37 subjek pada penelitian ini. Kasus BAVM didominasi oleh laki-laki (62,2%) dan lebih banyak pada pasien dewasa berusia >18 tahun (75,7%). Hampir seluruh pasien menggunakan jaminan kesehatan BPJS (94,6%) dan asal rujukan terbanyak adalah dari Jabodetabek (54,1%). Gejala terbanyak pada pasien adalah nyeri kepala 59,4%), diikuti dengan kesadaran terganggu (37,8%) dan kejang (35,1%). Temuan DSA tidak berbeda jauh dengan temuan MRA dan CTA. Hampir seluruh pasien memiliki feeding artery [DSA (97,3%); CTA dan MRA (100%)], mayoritas terdapat lokasi eloquent [DSA (67,6%); MRA (71,4%); CTA (80%)], berukuran sedang (3-6 cm) [DSA (59,5%); MRA (71,4%); CTA (40%)], dan memiliki drainase vena superficial [DSA (59,5%); MRA (71,4%); CTA (40%)]. Presentase grade SM terbanyak adalah grade III (31,6%), diikuti oleh grade IV (28,9%) dan grade II (21,1%).

Kesimpulan

Pengetahuan akan profil karakteristik klinis dan profil temuan pencitraan dapat memberikan pengetahuan lebih untuk membantu dokter menunjang diagnosis BAVM.

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Background

Brain Arteriovenous Malformation (BAVM) is a vascular anomaly in the brain that can cause various complications. The gold standard for detecting BAVM is digital subtraction angiography (DSA), but this modality is not widely available in Indonesia. This study was designed to provide an overview of the profile of clinical characteristics and findings from DSA, CT-Angiography (CTA), and MR-Angiography (MRA) in accordance with the Spezler-Martin Grade assessment.

Method

Medical record data and imaging results of BAVM cases with DSA accompanied/not by MRA or CTA examination were obtained from the Department of Neurosurgery, RSUPN Dr. Cipto Mangunkusumo (RSCM) in the 2018-2022 period. Cases that met the inclusion and exclusion criteria were included in this observational descriptive study.

Results

There was a total of 37 subjects in this study. BAVM cases are dominated by men (62.2%) and are more common in adult patients aged >18 years (75.7%). Almost all patients use BPJS health insurance (94.6%) and the highest number of referrals is from Jabodetabek (54.1%). The most common symptom in patients was headache, 59.4%), followed by impaired consciousness (37.8%) and seizures (35.1%). DSA findings do not differ much from MRA and CTA findings. Almost all patients had a feeding artery [DSA (97.3%); CTA and MRA (100%)], the majority had eloquent locations [DSA (67.6%); MRA (71.4%); CTA (80%)], medium-sized (3-6 cm) [DSA (59.5%); MRA (71.4%); CTA  (40%)], and had superficial venous drainage [DSA (59.5%); MRA (71.4%); CTAs (40%)].  The highest percentage of SM grade was grade III (31.6%), followed by grade IV (28.9%) and grade II (21.1%).

Conclusion

Knowledge of the profile of clinical characteristics and profile of imaging findings can  provide more knowledge to help doctors support the diagnosis of BAVM.

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"ABSTRAKTujuanTindakan bedah saraf, diduga dapat mengentikan atau memperlambat cedera otak sekunder, yang berhubungan dengan proses neuroinflamasi. Peneliti bertujuan untuk mengetahui peranan neuroinflamasi (Il-6) terhadap prognosis pasien cedera otak dan untuk mengetahui hubungan tindakan operasi dengan kondisi neuroinflamasi.MetodePenelitian ini bersifat prospektif observasional dengan desain cross sectional. Dari 40 pasien cedera otak yang dilakukan tindakan operasi, dilakukan pemeriksaan kadar Il-6 sebelum operasi dan 1 hari pasca tindakan operasi. GCS dinilai saat di UGD (GCS awal) dan sesudah tindakan operasi (GCS hari ke-7). GOS dinilai setelah bulan ke-1 dan bulan ke-3 pasca trauma. Kadar IL-6 sebelum operasi dan 1 hari pasca tindakan operasi dihubungkan dengan nilai GCS awal, GCS hari ke-7, GOS bulan ke-1 dan GOS bulan ke-3 untuk mengetahui hubungan tindakan operasi dengan proses neuroinflamasi dan nilai prognostiknya terhadap pasien cedera otak.GCS awal. GCS hari ke-7 dikelompokkan menjadi GCS <=8 dan GCS >8. GOS bulan ke-1 dan bulan ke-3 dikelompokkan menjadi GOS favorable (>3) dan unfavorable <=3.HasilKadar Il-6 awal berhubungan bermakna dengan GCS awal (p: 0.001) dengan OR 11.4 --> pasien dengan kadar Il-6 >100 pg/ml memiliki peluang 11.4 kali mendapatkan nilai GCS <=8. Terdapat perbedaan nilai median kadar Il-6 pasca operasi dibandingkan dengan pre operasi, dengan kecenderungan kadar Il-6 pasca operasi (median=35.55 pg/ml) lebih rendah daripada kadar Il-6 awal (median=76.74 pg/ml)Kadar Il-6 pasca operasi berhubungan bermakna dengan GCS hari ke-7 (p=0.006), dengan OR 24 --> pasien dengan Il-6 pre op <= 100 pg/ml memiliki peluang 24 kali memperoleh nilai GCS hari ke-7 >8. Kadar Il-6 pasca operasi berhubungan bermakna dengan GOS bulan ke-3 (nilai p= 0.016) dengan OR 11.6 --> pasien dengan kadar Il-6 <=100 pg/ml memiliki peluang sebesar 11.6 kali mencapai GOS bulan ke-3 favorable.SimpulanProses neuroinflamasi memiliki nilai prognostik pada pasien cedera otak, di mana maikin tinggi kadar Il-6 serum awal, makin buruk GCS awal pasien.Tindakan bedah saraf dapat menurunkan proses neuroinflamasi dan berhubungan dengan outcome GCS hari ke-7 (status kesadaran) pasca operasi dan GOS bulan ke-3 (kualitas hidup) yang lebih baik.

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ABSTRACTObjectivesNeurosurgical procedures are performed to stop or slow down the secondary brain injury. This study is aimed to determine the association of neuroinflammation with the prosnosis of brain injury patients and the association of neurosurgical procedure with the neuroinflammation.MethodThe study design is a prospective observation of 40 brain injuty patients who were operated. Examination were carried out top measured Il-6 serum level of pre and one day post operation on brain injury patients, and to analize therir association with GCS,GOS and neurosurgical procedures.ResultsThe Il-6 serum level pre surgery was significantly associated with initial GCS (p value=0.001 and OR 11.4). There was significant median difference of Il-6 post surgery compared with pre surgery, with a downward trend of Il-6 post surgery.The post operative Il-6 level was significantly associated with GCS 7 days post surgery (p=0.006), with OR 24, meaning that patients with post surgery level of Il-6 <= 100 pg/ml had 24 times chance of getting GCS 7 days post trauma >8. The post operative Il-6 serum was significantly associated with GCA 3 months post trauma (p value= 0.016) with OR 11.6, meaning that the patients with post operative Il-6 level <= 100 pg/ml has 11.6 times as much chance of reaching the 3 months post trauma GOS favorable.ConclusionNeuroinflammation may have prognostic values in brain injured patients. Neurosurgical procedures can decrease the neuroinflammation process and was associated with better conciousness state (GCS) and neurological outcome (GOS)."

"The study and modulation of cortical connections is a rapidly growing area in neuroscience. The first section of the book describes studies of cortical connections, modulation of cortical connectivity and changes in cortical connections with activities such as motor learning and grasping in primates. The second section covers the use of non-invasive brain stimulation to study and modulate cortical connectivity in humans. The last section describes changes in brain connectivity in neurological and psychiatric diseases, and potential new treatments that manipulate brain connectivity. This book provides an up-to-date view of the study of cortical connectivity, and covers its role in both fundamental neuroscience and potential clinical applications."

"ABSTRAKTujuan : Koreksi transatrial-transpulmonary tanpa transannular patch (TA-TP tanpaTAP) memiliki keuntungan berupa preservasi annulus katup pulmonal dan fungsiventrikel kanan, Namun sering terjadi gradien RV-PA dan pRV/LV ratio yang masihtinggi sehingga terjadi low cardiac output syndrome (LCOS). Penelitian ini bertujuanuntuk mencari batasan gradien RV-PA dan pRV/LV ratio yang merupakan nilai prediktifterbaik terhadap kejadian LCOS pascakoreksi tetralogi Fallot TA-TP tanpa TAP.Metode : Pada bulan Oktober 2012 sampai Maret 2013, sebanyak 30 pasien TF menjalanikoreksi TF TA-TP tanpa TAP (mean usia 8,37±7,90 tahun). Dilakukan pengukurangradien RV-PA dan pRV/LV ratio intraoperatif dan postoperatif di ICU. Evaluasi kejadianLCOS dilakukan selama perawatan di ICU. Sebelum pasien pulang, dilakukanpemeriksaan ekokardiografi untuk menilai gradien RV-PA, fungsi ventrikel kanan, defekseptum ventrikel residual, derajat regurgitasi katup pulmonal dan katup trikuspid.Hasil : Sebanyak 30 (100%) subjek penelitian memiliki z-value ≥ -1, menjalani koreksiTF TA-TP tanpa TAP. Mean gradien RV-PA intraoperatif adalah 21,13±10,60 mm Hgdan mean pRV/LV ratio intraoperatif adalah 0,53±0,14. Mean gradien RV-PA di ICUadalah 20,83±7,10 mmHg dan mean pRV/LV ratio di ICU adalah 0,49±0,10. Tidak terjadiLCOS pada 30 (100%) subjek penelitian sehingga tidak dapat dilakukan analisis untukmencari batasan nilai gradien RV-PA dan pRV/LV ratio sebagai nilai prediktif terbaikterhadap kejadian LCOS pascakoreksi TF TA-TP tanpa TAP. Mean gradien RV-PAsebelum subjek penelitian rawat jalan adalah 23,47±6,95 mmHg. Regurgitasi katuppulmonal ringan pada 15 (50%) subjek penelitian dan regurgitasi katup trikuspid trivialmildpada 16 (53%) subjek penelitian. Disfungsi ventrikel kanan ringan 3 (10%), sedang20 (67%) dan berat pada 7 (23%) subjek penelitian. Mean TAPSE postoperatif adalah1,03±0,19. DSV residual tidak dijumpai, aritmia tidak dijumpai, reoperasi dan mortalitastidak ada.Simpulan : Koreksi TF TA-TP tanpa TAP memberikan hasil operasi dini yang baik padapasien TF dengan z-value katup pulmonal ≥ -1, pRV/LV ratio < 0,5 dan gradien RV-PA <25 mmHg pascakoreksi.

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ABSTRACTObjective : The benefits of the transatrial-transpulmonary (TA-TP) without transannularpatch (TAP) correction of tetralogy of Fallot (TOF) are preservation of pulmonary valveannulus and right ventricular function. However, TA-TP without TAP correction of TOFhad a higher incidence of low cardiac output syndrome (LCOS) because of the high rightventricle and pulmonary artery (RV-PA) pressure gradient and right ventricle and leftventricle pressure (pRV/LV) ratio. The purpose of this study were to analyze the cut offvalue of RV-PA pressure gradient dan pRV/LV ratio as the best predictor value forpostoperative LCOS in TA-TP without TAP correction of TOF.Methods : Between Oktober 2012 and Maret 2013, 30 patients with TOF underwent TATPwithout TAP correction (mean age 8,37±7,90 years, range 1-27 years). At the end ofcorrection, all patients underwent intraoperative direct measurement of RV-PA pressuregradient and pRV/LV ratio. The patients were evaluated for postoperative LCOS at theIntensive Care Unit (ICU). All the patients underwent echocardiographic examinationbefore hospital discharge. This included investigation of the presence RV-PA pressuregradien, RV function, residual VSD, pulmonary and tricuspid valve insufficiency.Results : Thirty patients with pulmonary valve annulus z-value ≥ -1, underwent TA-TPwithout TAP correction of TOF. Mean intraoperative RV-PA pressure gradient was21,13±10,60 mmHg and mean intraoperative pRV/LV ratio was 0,53±0,14. Mean RV-PApressure gradient measured 24 hours after correction at the ICU was 20,83±7,10 mmHgand mean pRV/LV ratio measured at 24 hours after correction at the ICU was 0,49±0,10.No patient had LCOS, we could not analyze the cut off value of RV-PA pressure gradientand pRV/LV ratio as the best predictor value for postoperative LCOS in this study. Nopatient had residual VSD. Mean RV-PA pressure gradient before hospital discharge was23,47±6,95 mmHg. Fifteen (50%) patients had mild pulmonary valve insufficiency and16 (53%) patients had trivial-mild tricuspid valve insufficiency. Three (10%) patients hadmild RV dysfunction. Postoperative mean TAPSE was 1,03±0,19. No patient hadarrhythmia, reoperation and mortality in this study.Conclusions : The TA-TP without TAP correction of TOF was applied successfully in 30patients with pulmonary valve annulus z-value ≥ -1, post-correction RV-PA pressuregradient < 25 mmHg and pRV/LV ratio < 0,5."

"The purposes of the research are : (i) to describe the type of the noun Phrase (NP) functioning as the complement in the english clause ; (ii) to describe the structure of the continuents of the noun phrase functioning as the complement in the english clause; (iii) to describe the constituents that may be reduced, inserted, substituted, or transformed....."