Spatiotemporal electrophysiology of cerebral ischemia observed using chronic electrode array in auditory cortex

Author(s):  
M.T. Huberty ◽  
P. Tek ◽  
P.J. Rousche

Stroke research is of considerable societal value in an age in which the scourge is a leading cause of disability and the third-leading cause of death in the United States. While previous studies investigate the electrophysiology of stroke, none examine the long-term time-course of stroke recovery in the auditory cortex, the objective of this study. An electrode was implanted in the auditory cortex of two anesthetized Sprague-Dawley rats, stroke was induced in one of the subjects using photothrombosis, and daily electrical recordings were made while each subject was presented with a click stimulus every 500 ms. Peri-stimulus time histograms reveal that in the control subject, the second stimulus-evoked bursts peak decreased the day following implantation (Day 1) but returned almost to its Day 0 (day of surgery) value by Day 5, representing recovery from implantation trauma. The mean firing rate decreased logarithmically from its Day 0 value of 90 Hz to 10 Hz by Day 8, revealing decreasing electrode viability. In the stroke subject, the second stimulus-evoked bursts peak was undetected Day 1, but was detected again on Day 4, elucidating that the rat auditory cortex regains function as stroke recovery progresses.

1986 ◽  
Vol 64 (6) ◽  
pp. 683-688 ◽  
Author(s):  
Bernard Candas ◽  
Josée Lalonde ◽  
Maurice Normand

To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague–Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to0.73 ng rCRF∙min−1∙100 g BW−1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 ± 0.06 and 0.48 ± 0.05 mL∙min−1∙100 g BW−1). The volume of the first pool, 16.8 ± 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit. At steady state, the disposal rate represents only 3% of the CRF mass of the first compartment every minute. These results could explain the prolonged effects of CRF on pituitary-adrenocortical secretion.


2002 ◽  
Vol 283 (4) ◽  
pp. H1292-H1301 ◽  
Author(s):  
Ann L. Baldwin ◽  
Elizabeth B. Wiley ◽  
Abdu I. Alayash

Two “blood substitutes,” a diaspirin cross-linked human hemoglobin [bis(3,5 dibromosalicyl)fumarate, DBBF-Hb] and a bovine polymerized hemoglobin (PolyHbBv), advanced to clinical trials, are used in this study. Previously, we have shown that injection of DBBF-Hb into the rat circulation produces venular leakage and intestinal epithelial disruption. The purpose of this study was to determine whether PolyHbBv, currently approved for veterinary use in the United States, shows similar effects. In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with DBBF-Hb ( n = 6), PolyHbBv ( n = 5), cyanomet Hb (CNmet-DBBF-Hb), or HEPES-buffered saline with 0.5% bovine serum albumin (HBS-BSA) (controls, n = 7) for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. For DBBF-Hb, the mean leak number per micrometer venule length [2.41 ± 0.33 (±SE) × 10−3] was significantly greater than for PolyHbBv (0.53 ± 0.14 × 10−3), CNmet-DBBF-Hb (0.36 ± 0.14 × 10−3), and HBS-BSA (0.12 ± 0.08 × 10−3) ( P < 0.01). Corresponding quantities for leak area were 0.10 ± 0.03, 0.010 ± 0.003, 0.005 ± 0.003, and 0.02 ± 0.02 μm2/μm. In rats injected with DBBF-Hb ( n = 8), intestinal epithelial integrity was significantly compromised compared with those injected with PolyHbBv ( n = 5) or saline ( n = 6). These results indicate that intravascular PolyHbBv produces significantly less disruption of the intestinal exchange barrier than does DBBF-Hb, probably because the heme is not so easily oxidized.


2001 ◽  
Vol 91 (2) ◽  
pp. 709-716 ◽  
Author(s):  
E. B. Olson ◽  
C. J. Bohne ◽  
M. R. Dwinell ◽  
A. Podolsky ◽  
E. H. Vidruk ◽  
...  

We tested the hypothesis that unanesthetized rats exhibit ventilatory long-term facilitation (LTF) after intermittent, but not continuous, hypoxia. Minute ventilation (V˙e) and carbon dioxide production (V˙co 2) were measured in unanesthetized, unrestrained male Sprague-Dawley rats via barometric plethysmography before, during, and after exposure to continuous or intermittent hypoxia. Hypoxia was either isocapnic [inspired O2 fraction (Fi O2 ) = 0.08–0.09 and inspired CO2 fraction (Fi CO2 ) = 0.04] or poikilocapnic (Fi O2 = 0.11 and Fi CO2 = 0.00). Sixty minutes after intermittent hypoxia, V˙e orV˙e/V˙co 2 was significantly greater than baseline in both isocapnic and poikilocapnic conditions. In contrast, 60 min after continuous hypoxia,V˙e andV˙e/V˙co 2 were not significantly different from baseline values. These data demonstrate ventilatory LTF after intermittent hypoxia in unanesthetized rats. Ventilatory LTF appeared similar in its magnitude (after accounting for CO2 feedback), time course, and dependence on intermittent hypoxia to phrenic LTF previously observed in anesthetized, vagotomized, paralyzed rats.


2021 ◽  
Vol 10 (6) ◽  
pp. 1323
Author(s):  
Victor Yip ◽  
M. Violet Lee ◽  
Ola M. Saad ◽  
Shuguang Ma ◽  
S. Cyrus Khojasteh ◽  
...  

Polatuzumab vedotin (or POLIVY®), an antibody–drug conjugate (ADC) composed of a polatuzumab monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable dipeptide linker, has been approved by the United States Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma (DLBCL). To support the clinical development of polatuzumab vedotin, we characterized the distribution, catabolism/metabolism, and elimination properties of polatuzumab vedotin and its unconjugated MMAE payload in Sprague Dawley rats. Several radiolabeled probes were developed to track the fate of different components of the ADC, with 125I and 111In used to label the antibody component and 3H to label the MMAE payload of the ADC. Following a single intravenous administration of the radiolabeled probes into normal or bile-duct cannulated rats, blood, various tissues, and excreta samples were collected over 7–14 days post-dose and analyzed for radioactivity and to characterize the metabolites/catabolites. The plasma radioactivity of polatuzumab vedotin showed a biphasic elimination profile similar to that of unconjugated polatuzumab but different from unconjugated radiolabeled MMAE, which had a fast clearance. The vast majority of the radiolabeled MMAE in plasma remained associated with antibodies, with a minor fraction as free MMAE and MMAE-containing catabolites. Similar to unconjugated mAb, polatuzumab vedotin showed a nonspecific distribution to multiple highly perfused organs, including the lungs, heart, liver, spleen, and kidneys, where the ADC underwent catabolism to release MMAE and other MMAE-containing catabolites. Both polatuzumab vedotin and unconjugated MMAE were mainly eliminated through the biliary fecal route (>90%) and a small fraction (<10%) was eliminated through renal excretion in the form of catabolites/metabolites, among which, MMAE was identified as the major species, along with several other minor species. These studies provided significant insight into ADC’s absorption, distribution, metabolism, and elimination (ADME) properties, which supports the clinical development of POLIVY.


2006 ◽  
Vol 82 (4) ◽  
pp. 285-291 ◽  
Author(s):  
H. J. Lee ◽  
S. H. Kim ◽  
S. Y. Choi ◽  
Y. M. Gimm ◽  
J. K. Pack ◽  
...  

2006 ◽  
Vol 74 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Rachel Marion ◽  
Asiya Baishanbo ◽  
Gilles Gargala ◽  
Arnaud François ◽  
Philippe Ducrotté ◽  
...  

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.


2019 ◽  
Vol 7 (1) ◽  
pp. 117-121
Author(s):  
Herlambang Herlambang ◽  
Ave Olivia Rahman ◽  
Erny Kusdiyah

ABSTRACT Background: Infertility may give an impact on psychosocial. In Indonesia, the habit of consuming young dates is often done by couples to increase fertility. FSH is one of the factors that play a role in folliculogenesis. The lack of scientific evidence of young dates consumption effects on female reproduction has led to this study. This study aims to determine the levels of FSH hormone and the picture of ovarian tissue in mice after administration of young dates. Method: This study used an experimental design using 28 female Sprague-Dawley rats which were randomly divided into 4 groups. Group I to III was given young dates in successive doses: 17 mg, 34 mg, 68 mg per 200 grams of body weight and group IV was given distilled water. The treatment was carried out for 28 days. FSH levels were examined before treatment during the proestrus phase which was known from microscopic examination of rat vaginal swabs. The treatment begins during the proestrus phase. Result: The mean baseline and post-treatment FSH levels were 0.08 and 0.09 respectively Conclusion: There is no significant increase of FSH levels and FSH receptors as the effect of giving young dates (Phoenix Dactylifera) to female Sprague-Dawley rats Keywords: Dates, FSH, FSH receptors, Rats   ABSTRAK Latar Belakang: Infertilitas dapat memberikan dampak psikososial. Di Indonesia, kebiasaan mengkonsumsi kurma muda sering dilakukan oleh pasangan untuk meningkatkan kesuburan. Hormon FSH merupakan salah satu faktor yang berperan dalam folikelgenesis.  Belum adanya bukti ilmiah efek konsumsi buah kurma muda terhadap reproduksi wanita mendorong dilakukannya studi ini. Studi ini bertujuan mengetahui kadar hormon FSH dan gambaran jaringan ovarium pada tikus setelah pemberian kurma muda. Metode: Penelitian ini menggunakan desain ekperimental menggunakan tikus Sprague dawney betina sebanyak 28 ekor yang dibagi secara acak menjadi 4 kelompok. Kelompok I-III diberikan kurma muda dosis berturut -turut 17 mg, 34 mg, 68 mg per 200 gram BB dan kelompok IV diberikan aquadest. Perlakuan dilakukan selama 28 hari. Kadar hormon FSH diperiksa sebelum perlakuan saat fase proestrus yang diketahui dari pemeriksaan mikroskopis swab vagina tikus. Perlakuan dimulai saat fase proestrus. Hasil: Rerata kadar FSH baseline dan paska perlakuan adalah 0,08 dan 0,09 Kesimpulan: Tidak terdapat peningkatan yang signifikan kadar FSH dan reseptor FSH terhadap efek pemberian buah kurma muda (Phoenix Dactylifera) pada uterus tikus Spague Dawney Kata kunci : kurma, FSH, Reseptor FSH, tikus


2001 ◽  
Vol 90 (5) ◽  
pp. 2001-2006 ◽  
Author(s):  
D. D. Fuller ◽  
A. G. Zabka ◽  
T. L. Baker ◽  
G. S. Mitchell

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.


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