Search Results

You are looking at 1 - 2 of 2 items for

  • Author or Editor: Rakesh Shukla x
Clear All Modify Search
Restricted access

Melissa A. Lyons, Rakesh Shukla, Kejun Zhang, Gail J. Pyne, Meha Singh, Susan J. Biehle and Joseph F. Clark

Object. Cerebral vasospasm is a common cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). Previous research has shown that bilirubin oxidation products (BOXes) are present in the cerebral spinal fluid in patients with SAH-induced cerebral vasospasm and can contribute to vasoconstriction and vasospasm in vitro and in vivo. The events leading to cerebral vasospasm are not understood; however, one component of the occlusion may be due to vascular remodeling. In this study the authors have investigated the actions of BOXes, okadaic acid ([OA], a phosphatase inhibitor), and phorbol-12 myristate-13 acetate ([PMA], a protein kinase activator) on vascular smooth-muscle cell (VSMC) morphology and metabolism.

Methods. Immunohistochemical analysis was performed to assess VSMC morphology and α–smooth-muscle actin (αSMA) distribution following the application of BOXes, OA, or PMA. Changes in the level of lactate dehydrogenase (LDH) release and oxidative metabolism were also measured.

The BOXes, OA, or PMA caused VSMCs to change their shape and exhibit altered αSMA distribution. These treatments increased LDH release (p < 0.05), which is an index of increased cell stress. Oxidative metabolism significantly increased at low and high doses of BOXes, that is, 143 ± 8.5% and 180 ± 11.8%, respectively (p < 0.0001). Both PMA and OA also caused a significant increase in metabolism.

Conclusions. The authors concluded that BOXes, OA, and PMA alter VSMC morphology and metabolic activity, events that have been observed during vascular remodeling. Although the mechanism remains unclear, the results indicate that BOXes may play a role in the vascular remodeling that occurs following aneurysmal SAH.

Restricted access

Chad J. Morgan, Gail J. Pyne-Geithman, Edward C. Jauch, Rakesh Shukla, Kenneth R. Wagner, Joseph F. Clark and Mario Zuccarello

Object. A model of subarachnoid hemorrhage (SAH) in pigs was developed to investigate bilirubin concentration in cerebrospinal fluid (CSF) as a potential marker of sentinel SAH.

Methods. Seven male Yorkshire pigs received a 250-µl injection of either whole autologous arterial blood (four animals) or isotonic saline (three animals) into the cisternae magna in an effort to produce volumetrically a model of sentinel SAH and a control injection model, respectively. Cerebrospinal fluid volumes of 100 µl were then collected from both the lumbar cistern and cisternae magna at 1 to 2-hour intervals for a total of 24 hours postinjection. The CSF was then tested for bilirubin.

Mean concentrations of bilirubin (± standard deviation [SD]) obtained from the lumbar cistern 24 hours following the injection of blood or saline were 4.38 ± 1.04 µM in the SAH animals and 1.02 ± 0.05 µM in the controls. At 24 hours postinjection, mean concentrations (± SD) of cisternae magna bilirubin were 7.29 ± 1.33 ÉM and 1.33 ± 0.14 µM in the SAH animals and controls, respectively. In the SAH group, both the lumbar cistern and cisternae magna bilirubin concentrations differed significantly from baseline values 12 hours following SAH.

Conclusions. Elevated concentrations of CSF bilirubin can be detected following a low-volume SAH, and the production of bilirubin occurred over a predictable time course. Twelve hours after hemorrhage, an elevated CSF bilirubin concentration was an indicator of hemolysis occurring in the subarachnoid spaces. The presence of bilirubin in CSF is a potential marker for differentiating SAHs from traumatic lumbar punctures in humans.