High CSF transforming growth factor beta levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus.

BACKGROUND: Chronic communicating hydrocephalus is a common sequela of subarachnoid haemorrhage and develops when the flow and drainage of CSF are impaired after fibrosis in the subarachnoid space. Released by platelets into the CSF after subarachnoid haemorrhage, transforming growth factor (TGF)beta1/beta2 are potent fibrogenic agents that may promote post-haemorrhagic fibrosis and chronic communicating hydrocephalus. METHODS: Temporal changes in total (latent plus active) TGFbeta1/beta2 CSF levels of post-haemorrhage patients developing acute hydrocephalus were measured using ELISA to discover if titres were higher in patients that subsequently developed chronic communicating hydrocephalus, compared with those that did not. RESULTS: Mean (SD) CSF levels of total TGFbeta1 were 97 (42) pg/ml and total TGFbeta2 were 395 (39) pg/ml in control patients with (non-haemorrhagic) hydrocephalus. For days 1-5 post-subarachnoid haemorrhage (dph), levels of 1427 (242) pg/ml and 976 (191) pg/ml were seen for total TGFbeta1 and TGFbeta2, respectively. Beyond 5 dph, total TGFbeta1/beta2 levels declined but remained significantly elevated (p<0.01) above control patient values for at least 19 dph. Haemorrhagic patients that went on to develop chronic communicating hydrocephalus had significantly higher levels of total TGFbeta1 (p<0.01) and TGFbeta2 (p<0.05) between 1 and 9 dph, compared with those of haemorrhagic patients that did not. CONCLUSIONS: Acutely measured levels of TGFbeta1/beta2 in the CSF of patients with subarachnoid haemorrhage are thus potential prognostic biomarkers for the subsequent development of chronic communicating hydrocephalus, indicating likely dependency on CSF shunting.

Hindbrain hernia masquerading as postpartum subarachnoid haemorrhage.

A 29-year-old postpartum lady presented with a headache suggestive of subarachnoid haemorrhage. Investigations were negative for sources of haemorrhage, but revealed a hindbrain hernia. Hindbrain hernia should be considered as a cause of headache postpartum, as repeated Valsalva manoeuvres performed during vaginal delivery may further aggravate tonsillar decent.

Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources.

Transforming growth factor-beta1 (TGF-beta1) is a fibrogenic cytokine that is involved in postinjury repair and is implicated in the etiology of postsubarachnoid hemorrhage (SAH) chronic communicating hydrocephalus. TGF-beta1 was measured by enzyme-linked immunosorbant assay (ELISA) in sequential samples of cerebrospinal fluid (CSF) in 11 patients with hydrocephalus after SAH; levels were seen to be biphasically elevated and sources were investigated. TGF-beta1 levels were compared with albumin levels that estimated CSF blood content. Control samples from nonhemorrhagic hydrocephalics were tested similarly. Mean total TGF-beta1 levels were elevated to 4400+/-3435 (+/-SD) pg/mL greater than control levels of 97+/-42 at 1 to 2 days posthemorrhage. Thereafter, levels fell to 714+/-401 by 5 to 6 days posthemorrhage, then rose to a second peak of 1667+/-774 at 9 to 10 days posthemorrhage, remaining significantly increased until 19 days posthemorrhage (P = 0.007). The first peak probably derived from extravasated platelets and correlated with increased albumin levels in the CSF. The second TGF-beta1 peak rose greater than CSF albumin levels that had stabilized at this time, and thus was attributed to a tissue-specific response rather than a re-bleed. TGF-beta1 was detected in the choroid secretory epithelium from controls, but levels were greater in SAH patients at 10 to 12 days posthemorrhage. The authors conclude that the elevated levels of TGF-beta1 in CSF after SAH are derived initially from blood and later from endogenous sources such as the choroid plexus.

Brain abscesses associated with pulmonary arteriovenous malformations.

We present three patients with brain abscesses who also had pulmonary arteriovenous malformations (AVMs). All patients had hereditary haemorrhagic telangiectasia (Osler's Disease). It is probable that the lung AVMs contributed to the development of the brain abscesses by allowing bacteria easier access to the systemic circulation through a right to left pulmonary vascular shunt, bypassing the filtering action of the pulmonary capillaries. In addition, one patient required a period of postoperative ventilation using PEEP, which may have exacerbated the shunt through the lung AVM and led to difficulty in weaning her from the ventilator.

Nonexpression of CD15 by neoplastic glia: a barrier to metastasis?

Cluster of differentiation 15 (CD15) monoclonal antibodies recognise cell adhesion molecules on the surface of many cells including normal astrocytes and metastatic carcinoma cells. The CD15 epitope (fucosyl-N-acetyl-lactosamine), an adhesive oligosaccharide, functions as a ligand for the selectin family of membrane receptors. These include CD62, a cytokineinducible glycoprotein found in platelets and endothelial cells. CD15 is one of a series of putative adhesion molecules expressed in nervous tissue. Selectin-carbohydrate interactions have been implicated in the metastatic spread of cancer cells. We have immunostained a variety of cultured human brain tumours, three cell lines derived from experimental rat gliomas, two specimens of cultured human foetal astrocytes, two metastatic carcinoma cell lines and human umbilical vein endothelial cells (HUVEC) using two monoclonal antibodies which recognise CD15. While all of the animal glioma cells were positive for CD15, only two human glioma cell lines, derived from an anaplastic astrocytoma and a glioblastoma multiforme, respectively, displayed limited reactivity. Chromium radiolabel binding assays of CD15-positive and -negative cell lines including glioma and carcinoma-derived cells, using HUVEC as an attachment substrate, were carried out in the presence and absence of CD15 monoclonal antibody. The level of adhesion of neoplastic cells to HUVEC not only corresponded to CD 15 expression but application of anti-CD 15 monoclonal antibodies considerably reduced adhesion. We postulate that the absence of CD15 on human glioma cells may explain, to some extent, the general failure of intrinsic brain tumours to metastasis by precluding the adhesion of circulating neoplastic glia to 'target' organ endothelium.

Differential binding of anti-CD44 on human gliomas in vitro.

Recent studies have shown that the membrane glycoprotein, CD44, is expressed on both normal and neoplastic astrocytes. Moreover, CD44 has been shown to recognise the receptor for hyaluronic acid (HA), an extracellular matrix protein thought to be involved in tumour invasion. The present study has established, by immunocytochemical staining, that CD44 is present on the majority of cells in long and short term cultures derived from astrocytic gliomas. In glioblastoma multiforme, medulloblastoma, ependymoma and dysembryoplastic neuroepithelial tumour, however, staining is either absent or restricted to isolated cells. This differential binding suggests that HA receptor expression may be related to (a) the cell cycle and (b) local invasiveness of brain tumours.