Increased expression of matrix metalloproteinase-9 and hepatocyte growth factor in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus.
BACKGROUND
In approximately 60% of infants with posthemorrhagic hydrocephalus (PHH), ventricular dilation resolves by unknown intrinsic mechanisms, without the need for a shunt operation. A pathological hallmark of PHH is extensive deposition of extracellular matrix (ECM) proteins in the subarachnoid space. Our previous study revealed that matrix metalloproteinase (MMP)-9, which degrades ECM proteins, may play an important role in the resolution of ventricular dilation. MMP-9 is known to be induced by hepatocyte growth factor (HGF) in various cell lines.


OBJECTIVE
The aim of this study is to confirm our earlier finding that MMP-9 contributes to the resolution of PHH, and to investigate whether HGF also contributes to this process.


METHODS
Cerebrospinal fluid (CSF) samples were collected from 13 infants who developed ventricular dilation after intraventricular hemorrhage (IVH). Of these infants, 9 exhibited resolution of ventricular dilation without shunt operation; however, 4 infants had to be treated with shunt operation. The CSF levels of MMP-9 and HGF were measured using an enzyme immunoassay.


RESULTS
Significantly higher CSF levels of MMP-9 and HGF were detected in patients in whom the ventricular dilation resolved without shunt operation than in those with progressive ventricular dilation (MMP-9: median, 128ng/ml; range, 47-900ng/ml vs median, 50ng/ml; range, 12-110ng/ml; p<0.05; HGF: median, 2.42ng/ml; range, 0.81-7.04ng/ml vs median, 1.42ng/ml; range, 0.67-3.87ng/ml; p<0.05).


CONCLUSIONS
Our results indicate that MMP-9 and HGF may participate in the resolution of ventricular dilation following IVH.
Okamoto
Toshio
T
Department of Pediatrics, Asahikawa Medical College, Hokkaido, Japan. toshio5p@asahikawa-med.ac.jp <toshio5p@asahikawa-med.ac.jp>
Takahashi
Satoru
S
Nakamura
Eiki
E
Nagaya
Ken
K
Hayashi
Tokitsugi
T
Shirai
Masaru
M
Fujieda
Kenji
K
D002552:Cerebral Ventricles / Q000473:pathology; D006470:Hemorrhage / Q000209:etiology*; D017228:Hepatocyte Growth Factor / Q000134:cerebrospinal fluid*; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid* / Q000150:complications; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000134:cerebrospinal fluid*; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*
D017228:Hepatocyte Growth Factor; D020780:Matrix Metalloproteinase 9