thromboxane-b2 and Craniocerebral-Trauma

Methylprednisolone was recently reported to significantly improve motor and sensory function after acute spinal cord injury in patients. Our study was designed to determine whether methylprednisolone exerts a beneficial effect after head injury. Diethyl ether-anesthetized rats were assigned to receive surgery with no cranial impact and no methylprednisolone (group A, n = 13); surgery with no cranial impact and intraperitoneal methylprednisolone (greater than or equal to 60 mg/kg) (group B, n = 8); surgery with cranial impact and no methylprednisolone (group C, n = 8, and group E, n = 8); or surgery with cranial impact and methylprednisolone (greater than or equal to 60 mg/kg) (group D, n = 15, and group F, n = 13). Neurologic severity score was determined at 1, 2, 4, and 24 h (when appropriate) after injury, and brain tissue eicosanoid levels and cerebral edema were determined when the animals were killed (4 h after injury in groups C and D and 24 h after injury in groups E and F). Treatment with methylprednisolone did not improve neurologic severity score or edema formation and did not alter brain tissue levels of prostaglandin E2, thromboxane B2, or 6-keto-prostaglandin F1 alpha at any time period. The authors conclude that methylprednisolone does not exert a beneficial effect on brain tissue edema or functional activity after cranial impact in rats.

Topics: Animals; Brain; Brain Edema; Craniocerebral Trauma; Male; Methylprednisolone; Nervous System Diseases; Prostaglandins; Rats; Thromboxane B2

Head injury was induced in rats by a weight drop device, falling over the left hemisphere. The rats were killed at 15 min, 4 h, and 24 h after injury. Cortical slices were taken from the injured zone, from the corresponding region of the contralateral hemisphere, and from the frontal lobe of both hemispheres. These cortical slices were incubated in the presence of a fluorescent phospholipid analogue, 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)aminocaproylphosphatidylch oli ne (C6-NBD-PC) which is a substrate for phospholipase A2 (PLA2) in intact cells. The interaction of this substrate with cells produces only one fluorescent product, the fatty acid C6-NBD-FA, released from the 2-position of C6-NBD-PC. Thus, the level of C6-NBD-FA produced is a direct measure of PLA2 activity. Fifteen minutes after trauma, a 75% increase of PLA2 activity was found in the injured zone. At 4 h, the frontal lobe of the contused, left hemisphere had elevated PLA2 activity, as well as the injured zone (92 and 81%, respectively). At 24 h, PLA2 activity at the site of injury was 245% of sham. In the right, noninjured zone, no significant changes in PLA2 activity were noticed during the entire time course of the experiment. Prostaglandin E2 (PGE2) was extracted from the same cortical slices as those used for PLA2 activity measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Viscosity; Brain; Craniocerebral Trauma; Dextrans; Dinoprostone; Enzyme Activation; Fluorescent Dyes; In Vitro Techniques; Male; Phosphatidylcholines; Phospholipases; Phospholipases A; Phospholipases A2; Rats; Rats, Inbred Strains; Thromboxane B2; Time Factors

Head injury was induced in the left hemisphere of rats. The rats were killed at various time intervals after trauma (immediately, 15 min, 1 and 18 h, and 4 and 10 days), and the rates of synthesis and release of prostaglandin PGE2, 6-keto-PGF1 alpha, and thromboxane TXB2 from cortical slices of both hemispheres were studied. The rate of synthesis of PGE2 after 18 h was six and four times higher than control in the contused and contralateral hemispheres, respectively. By 10 days post-trauma, both hemispheres had normal rate of PGE2 release. TXB2 and 6-keto-PGF1 alpha synthetases were affected already 15 min after the injury, and a similarly elevated rate of synthesis was found in both hemispheres. The maximal effect was detected after 1 or 18 h with return to normal after 4 or 10 days for TXB2 and 6-keto-PGF1 alpha, respectively. Tissue specific gravity was determined for both hemispheres using linear gradient columns. The results of these determinations indicate that development of edema occurs in the contused hemisphere as early as 15 min post trauma; it reaches its maximal level at 18 h and returns to normal at 10 days. Arterial pressure was monitored, and a transient increase was found at 10 min post trauma. We suggest that the production of edema after brain injury may be related to the increased rate of PGE2 and PGI2 synthesis, which occurs at similar time intervals after injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Brain; Brain Edema; Craniocerebral Trauma; Dinoprostone; Male; Prostaglandins; Prostaglandins E; Rats; Thromboxane B2

Plasma levels of thromboxane A2 and prostacyclin have been elevated during experimental acute respiratory failure (ARDS). The present study evaluates the relationship of plasma levels of thromboxane A2 and prostacyclin, measured by radioimmunoassay as the stable metabolites thromboxane B2 (TxB) and prostaglandin 6-K-F1 alpha (PGI) to the incidence of clinical ARDS. Sixty-seven consecutive patients at risk for ARDS were studied prospectively. TxB, PGI, platelet, and leukocyte counts were measured daily for up to 5 days. Of 55 patients without cerebral injury, 25 (45%) developed ARDS, and 30 did not. Of 12 patients with cerebral injury, none developed ARDS. This difference was highly significant (P less than 0.01). TxB was increased and age lower with head injury (P less than 0.05). PGI was significantly lower in ARDS (110 +/- 32 vs 227 +/- 211 pg/ml, P less than 0.05), and mean TxB was unchanged. TxB was increased in age greater than 60 and decreased with prostaglandin inhibitors. ARDS was significantly associated with TxB greater than 70 pg/ml, PGI below the detectable level of 103 pg/ml, TxB/PGI ratio greater than 0.7, and age greater than 60 years. Peak TxB occurred before or simultaneously with onset of ARDS in 68%. Leukocytes were decreased in ARDS (8.6 +/- 4 vs 11.1 +/- 4.4 X 10(3)/mm3) and platelets were unchanged. ARDS was decreased with steroid therapy. Elevated TxB is related to a high incidence of ARDS. Elevated PGI may protect against ARDS. Cerebral injury patients in this study were resistant to ARDS in spite of increased TxB.

Topics: 6-Ketoprostaglandin F1 alpha; Adrenal Cortex Hormones; Age Factors; Craniocerebral Trauma; Epoprostenol; Female; Humans; Male; Platelet Count; Prostaglandin Antagonists; Respiratory Insufficiency; Thromboxane B2; Thromboxanes