Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors
Highlights
► We evaluated astrocyte activation and inflammation involvement in human epilepsy samples. ► High GFAP is associated with increased AQP4, CX43, m-calpain, and L-type Ca2+ channels. ► Kir4.1, dystrophin, and α-syntrophin are decreased in human epilepsy. ► Inflammatory markers and glutamate receptors/subunits are also increased. ► Astrocyte-related inflammation may be a significant target for new epilepsy therapy.
Section snippets
Background
Epilepsy is a chronic brain disorder, defined by spontaneous recurrent seizures. Temporal lobe epilepsy (TLE), the most common form in adults, is generally characterized by a unilateral temporal lobe seizure foci (Cascino, 2005, Sharma et al., 2007). Due to the lack of effective pharmacotherapies, a relatively large percentage of the TLE patients suffer from medically intractable seizures. As a result, invasive resection of the seizure focus is often recommended as a final alternative to
Acquisition of human epileptic samples
Patient samples were collected following temporal lobe resection performed as treatment for refractory TLE. Patient consent was obtained for tissue use before surgery. All patients included in this study were diagnosed as epileptic according to the criteria defined by the International League Against Epilepsy (Commission of Classification and Terminology of the International League Against Epilepsy). Patients were evaluated based on clinical history, physical examination, ictal EEG recording,
Demographic and clinical characteristics of subjects
The mean age of the epilepsy patients was 33.5 ± 8.73 years, with three men and three women in the experimental group (Table 2). The mean duration of seizure recurrence was 8.9 ± 3.06 years. Clinical information from all patients is summarized in Table 2. Epilepsy patients experienced seizure recurrence for at least 5 years, with three in six having recurrences for more than 10 years. The sudden death control group consisted of three men, with an average age of 30.90 ± 8.65 years. Statistical analysis
Discussion
Histological and molecular changes associated with TLE are complex and still poorly defined. Neuronal hypertrophy and increased expression of pro-inflammatory factors are hallmarks of TLE and generally suggest astrocytic activation. In this regard, our work has confirmed previous findings. Changes in extracellular osmotic and ionic gradients have been implicated as a mechanism by which dysfunctional astrocytes may promote neuronal hyperexcitability in TLE (Yang et al., 2010). Hypo-osmotic
Disclosure
None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent.
Acknowledgements
This work was supported in part by the grants from the National Institute of Neurological Disorders and Stroke (NS-31622, NS-38146, and NS-41088) and the South Carolina Spinal Cord Injury Research Fund.
References (38)
- et al.
Cell swelling precedes seizures induced by inhibition of astrocytic metabolism
Epilepsy Res
(2008) - et al.
Neuronal activity triggers calcium waves in hippocampal astrocyte networks
Neuron
(1992) - et al.
Induction of astrocytic cyclooxygenase-2 in epileptic patients with hippocampal sclerosis
Neurochem Int
(2003) - et al.
Hippocampal connexin 43 expression in human complex partial seizure disorder
Exp Neurol
(1997) - et al.
The role of cytokines and growth factors in seizures and their sequelae
Prog Neurobiol
(2001) - et al.
L-type voltage-gated calcium channels modulate kainic acid neurotoxicity in cerebellar granule cells
Brain Res
(1999) - et al.
Cell swelling, seizures and spreading depression: an Impedance study
Neuroscience
(2006) - et al.
Inflammation and prevention of epileptogenesis
Neurosci Lett
(2011) - et al.
Reactive astrocytes: cellular and molecular cues to function
Trends Neurosci
(1997) - et al.
Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat
Brain Res Mol Brain Res
(2000)
Why mesial temporal lobe epilepsy with hippocampal sclerosis is progressive: uncontrolled inflammation drives disease progression?
J Neurol Sci
The expression of transforming growth factor-beta1 (TGF-β1) in hippocampal neurons: a temporary upregulated protein level after transient forebrain ischemia in the rat
Brain Res
Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus
J Neurochem
Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy
Eur J Neurosci
Neuropathologic and clinical features of human medial temporal lobe epilepsy
J Clin Neurol
Astrocyte-neuron interactions: implications for epilepsy
Neurology
Temporal lobe epilepsy: more than hippocampal pathology
Epilepsy Curr
Cellular injury and neuroinflammation in children with chronic intractable epilepsy
J Neuroinflammation
Does glutamate released by astrocytes cause focal epilepsy?
Epilepsy Curr
Cited by (164)
Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders
2024, Neurochemical ResearchMetabotropic glutamate receptors (mGluRs) in epileptogenesis: An update on abnormal mGluRs signaling and its therapeutic implications
2024, Neural Regeneration ResearchThe cerebral lymphatic drainage system and its implications in epilepsy
2024, Journal of Neuroscience Research